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Patterning and Cell Type Specification in the Developing CNS and PNS
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Contributors
Part I: Induction and patterning of the CNS and PNS
1 - Morphogens, patterning centers, and their mechanisms of action
1.1 General principles of morphogen gradients
1.1.1 History of the morphogen and morphogenetic field
1.1.2 How morphogen gradients pattern tissues
1.1.3 How morphogens are distributed
1.1.4 How morphogen signaling is transduced and interpreted
1.1.5 How morphogen gradients are converted into sharp boundaries
1.1.6 Summary-general principles of morphogen gradients
1.2 Local signaling centers and probable morphogens in the telencephalon
1.2.1 Early forebrain patterning
1.2.2 The RPC
1.2.3 The telencephalic roof plate and cortical hem
1.2.4 The antihem
1.3 BMPs as morphogens in telencephalic patterning
1.3.1 Performance objectives for a BMP gradient in the dorsal telencephalon
1.3.2 Midline expression and homeogenetic expansion of BMP production
1.3.3 BMP signaling gradient in the dorsal telencephalon
1.3.4 BMPs as dorsal telencephalic morphogens
1.3.5 Linear conversion of BMP signaling by cortical cells
1.3.6 Nonlinear conversion of BMP signaling by DTM cells
1.3.7 Summary-the BMP signaling gradient
1.4 FGF8 as a morphogen in telencephalic patterning
1.5 Interactions among signaling centers in telencephalic patterning
1.5.1 FGF8, Shh, and BMP signaling
1.5.2 Cross-regulation of BMP, FGF, and WNT signaling
1.5.3 Interactions of Shh, FGFs, and Gli3
1.6 Morphogens in human brain disease
1.6.1 Holoprosencephaly and Kallmann syndrome
1.6.2 Gradients in holoprosencephaly neuropathology
1.6.3 Gradients in other human brain disorders
References
2 - Telencephalon patterning
2.1 Introduction
2.2 Telencephalon induction
2.2.1 The anterior neural ridge
2.2.2 FGF signaling
2.2.3 Wnt antagonism
2.2.4 Interactions of low Wnt with FGFs and BMPs
2.3 Overview of early telencephalic subdivisions
2.4 Establishing dorsal versus ventral domains
2.4.1 Shh and Gli3, two key players
2.4.2 Foxg1 and FGFs cooperatively promote ventral development
2.4.3 Establishing the dorsal telencephalic domain
2.4.4 Sharpening the dorsal-ventral border
2.4.5 The olfactory bulbs
2.5 Boundary structures as organizing centers and CR cell sources
2.5.1 Nomenclature of domains in the early telencephalic neuroepithelium
2.5.2 Specification of the hem and the antihem
2.5.2.1 Molecular mechanisms that act to position and specify the cortical hem
2.5.2.2 Molecular mechanisms that act to specify and position the antihem
2.5.3 Cajal-Retzius cells arise from four telencephalic boundary structures
2.5.4 Organizer functions of telencephalic boundary structures
2.5.4.1 Rostral signaling center/septum
2.5.4.1.1 Hem
2.5.4.2 Antihem
2.6 Subdividing ventral domains
2.6.1 The striatum and pallidum
2.6.2 The amygdala
2.6.3 An evolutionary perspective for how the neocortex arose
2.6.4 Lineage and fate mapping in the ventral telencephalon
2.7 Conclusions
Acknowledgments
References
3 - Area patterning of the mammalian neocortex
3.1 Introduction
3.1.1 Basic principles
3.1.2 Classic neocortical area patterning models
3.2 Indications that intrinsic mechanisms pattern the neocortical primordium
3.3 Morphogens impart position to the neocortical primordium
3.3.1 Morphogen signaling
3.3.2 Neocortical patterning by FGFs
3.3.3 Fgf8 regulates neocortical guidance of thalamic axons
3.3.4 Neocortical patterning by the cortical hem
3.4 Patterning genes downstream of morphogen signaling
3.4.1 Emx2 and Pax6
3.4.2 Dmrt5/Dmrta2
3.4.3 Couptf1/Nr2f1
3.4.4 Sp8
3.4.5 Pbx
3.5 Do neocortical areas arise from dedicated progenitor cell pools?
3.5.1 Transcription factors known to pattern the NP appear in gradients, not domains
3.5.2 Mapping the cortical primordium with forebrain enhancers
3.6 The influence of thalamic innervation
3.6.1 Guidance of thalamocortical axons and area formation
3.6.2 Thalamic innervation determines the function of a cortical area
3.6.3 Effects of thalamocortical afferents on area size and cortical progenitor cells
3.6.4 Thalamic dependence of an area-specific feature
3.6.5 Two mechanisms united
3.7 Spontaneous activity and neocortical patterning
3.8 Conservation of patterning mechanisms among different mammalian species
3.9 Conclusions
References
4 - Patterning of thalamus
4.1 Introduction
4.2 Insights into diencephalic patterning
4.2.1 Columnar and neuromeric models
4.2.2 Morphologic segmentation of the diencephalon in the prosomeric model
4.2.3 Molecular regionalization of the diencephalon
4.2.3.1 Prosomere 1
4.2.3.2 Prosomere 2: the epithalamic domain
4.2.3.3 Prosomere 3
4.3 Prosomere 2: the thalamic domain
4.3.1 Cell lineages in the p2 alar plate
4.3.2 Signaling molecules during the initial patterning phase
4.3.2.1 Shh
4.3.2.2 Wnt
4.3.2.3 Fibroblast growth factor
4.3.3 Transcription factor control for neuronal identity
List of acronyms and abbreviations
References
5 - Midbrain patterning: polarity formation of the tectum, midbrain regionalization, and isthmus organizer
5.1 Introduction: brief description about midbrain
5.2 Tectum laminar formation
5.3 Optic tectum as a visual center for the lower vertebrate
5.3.1 Retinotectal projection in a retinotopic manner
5.3.2 Polarity formation in the optic tectum
5.4 Development of midbrain from the mesencephalic brain vesicle
5.4.1 Transcription factors that determine the midbrain
5.4.2 Midbrain-hindbrain boundary formation
5.4.3 Diencephalon-mesencephalon boundary formation
5.4.4 Dorsoventral patterning in the midbrain
5.5 Isthmus organizer
5.5.1 Isthmus emanates organizing signal
5.5.2 Competence of the neural tube to Fgf8 signaling is determined by preexisting transcription factors
5.5.3 Intracellular signal transduction
5.5.4 How tectum and cerebellum are organized by isthmus organizing signal?
5.6 Concluding remarks
List of abbreviations of genes and molecules
List of abbreviations (general)
Glossary
References
6 - Cerebellar patterning
6.1 Introduction
6.2 Early formation of cerebellum
6.2.1 Morphogenetic aspect of first steps of cerebellar formation
6.2.2 Molecular mechanisms underlying initial formation of cerebellum
6.3 Three types of cerebellar patterning in adult mammals
6.3.1 Cerebellar anterior-posterior patterning
6.3.1.1 Lobes
6.3.1.2 Lobules (I-X)
6.3.1.3 Functional roles of lobes
6.3.2 Cerebellar medial-lateral patterning
6.3.2.1 Parasagittal zones
6.3.2.2 Parasagittal stripes
6.3.2.3 Correspondence between parasagittal zones and parasagittal stripes
6.3.2.4 Functional roles of parasagittal zones and stripes
6.3.3 Cerebellar outer-inner patterning
6.3.3.1 The molecular layer
6.3.3.2 The Purkinje cell layer
6.3.3.3 The granular layer
6.3.3.4 The white matter
6.3.3.5 The cerebellar nuclei
6.3.3.6 Roles of cerebellar outer-inner patterning
6.4 Formation of cerebellar patterning
6.4.1 Formation of cerebellar anterior-posterior patterning
6.4.1.1 Formation of lobes and lobules
6.4.1.2 Cellular mechanisms underlying the formation of lobes and lobules
6.4.2 Formation of cerebellar medial-lateral patterning
6.4.2.1 Formation of parasagittal zones
6.4.2.2 Cellular and molecular mechanisms underlying the formation of parasagittal zones
6.4.2.3 Formation of parasagittal stripes
6.4.2.4 Critical roles of Purkinje cell birth date in the formation of embryonic and adult parasagittal stripes and parasagittal zones
6.4.3 Formation of cerebellar outer-inner patterning
6.4.3.1 Formation of the molecular layer
6.4.3.2 Formation of the Purkinje cell layer
6.4.3.3 Formation of the granular layer
6.4.3.4 Formation of the white matter and the cerebellar nuclei
6.4.3.5 Mechanisms underlying the control of neuronal migration
6.4.3.6 The deficits of neuronal migration by exposure to toxic substances and natural environmental factors result in abnormal O-I ...
References
7 - Patterning and generation of neural diversity in the spinal cord
7.1 Introduction
7.2 Spatial signals and the generation of neuronal diversity
7.2.1 Dorsoventral patterning and the induction of progenitor domains
7.2.1.1 Induction of neural progenitor ventral fate: Shh signaling
7.2.1.2 Induction of dorsal progenitor fate: Bmp and Wnt signaling
7.2.2 Rostrocaudal patterning and regional identity
7.2.2.1 Rostrocaudal antiparallel signaling
7.2.2.2 Hox function in neuronal diversity
7.3 Transcription factor combinatorial codes
7.3.1 Transcriptional codes in spinal cord progenitor fate
7.3.2 Transcription factor combinatorial codes in the diversification of postmitotic motor neurons
7.3.3 Transcriptional signatures in spinal cord interneuron diversification
7.4 Local signals and cell-cell interactions
7.4.1 The role of notchdelta signaling in interneuron and motor neuron subtype specification
7.4.2 Retinoid signaling in motor neuron subtype specification
7.5 Temporal signals in the specification of spinal cord glia
7.5.1 Specification of oligodendrocytes
7.5.2 Astrogenesis in the spinal cord
7.6 Application of spinal cord developmental programs to advance therapies for human diseases
7.7 Conclusions
List of abbreviations
Glossary
References
8 - Formation and maturation of neuromuscular junctions
8.1 Introduction
8.2 The neuromuscular junction is comprised of three cell types
8.3 Origin and initial interaction among cells that form the neuromuscular junction
8.4 Formation of a differentiated postsynaptic membrane: the agrin-MuSK hypothesis
8.5 Interplay between agrin and ACh in sculpting the postsynaptic region
8.6 Molecules involved in nAChR prepatterning
8.7 Additional molecules important for clustering and stabilizing developing neuromuscular junctions
8.8 Synapse elimination at the neuromuscular junction
8.9 Synapse elimination: structural and functional changes at neuromuscular junctions
8.10 Synapse elimination: activity-dependent competition and molecular mechanisms
8.11 Synapse elimination: role of T/PSCs
8.12 Maturation and maintenance of neuromuscular junctions
8.13 Summary
List of abbreviations
References
9 - Neural induction of embryonic stem/induced pluripotent stem cells
9.1 Introduction
9.2 Introduction to embryonic stem cells and induced pluripotent stem cells
9.2.1 Reprogramming
9.2.2 Discovery of induced pluripotent stem cells
9.3 Neural induction
9.4 Patterning of neural progenitors
9.4.1 Neuronal progenitor specification along the D-V axis
9.4.2 Neuronal progenitor specification along the A-P axis
9.4.3 Patterning using multiple morphogens gradients
9.4.4 Temporal patterning
9.5 Differentiation to specific regional identities
9.5.1 Differentiation to forebrain cell types
9.5.1.1 Cerebral cortex
9.5.1.2 Hippocampus
9.5.1.3 Basal ganglia
9.5.2 Differentiation to midbrain cell types
9.5.3 Differentiation to hindbrain cell types
9.5.4 Differentiation to spinal cord cell types
9.6 Differentiation to neural crest stem cells
9.7 Differentiation to astrocytes and oligodendrocytes
9.7.1 Astrocytes
9.7.2 Oligodendrocytes
9.8 Direct conversion of fibroblasts to induced neurons
9.9 Conclusion
Acknowledgment
References
10 - Brain organoids as a model system for human neurodevelopment in health and disease
10.1 Recapitulation of in vivo neurodevelopment
10.1.1 Stage I: Neural induction and patterning
10.1.2 Stage II: Lumen formation and apical-basal polarity
10.1.3 Stage III: Proliferation of neural progenitors, interkinetic nuclear motion, and cortical expansion
10.1.4 Stage IV: Neurogenesis, cortical layers formation, and neuronal migration
10.1.5 Stage V: Neuronal maturation and network activity
10.1.6 Evolutionary neurodevelopmental biology in organoids
10.2 Organoids for neurodevelopmental disease modeling
10.2.1 Modeling diseases associated with brain structure
10.2.1.1 Microcephaly (small brains)-genetic mutations
10.2.1.2 Microcephaly-ZIKA virus, mechanisms, and potential therapies
10.2.1.3 Macrocephaly (large brains)
10.2.1.3.1 Lissencephaly (smooth brain)
10.2.2 Modeling of neuropsychiatric disorders
10.2.2.1 Autism spectrum disorders and schizophrenia
Acknowledgments
References
11 - Formation of gyri and sulci
11.1 Introduction
11.2 Timing of the formation of gyri and sulci
11.3 Cortical folding in evolution
11.4 Cellular mechanisms of cortical folding
11.4.1 Outer subventricular zone and basal progenitors
11.4.2 Gene expression profiles
11.4.3 Human- and primate-specific genes
11.4.4 Differential growth and proliferation
11.4.4.1 Cell cycle and the length of the neurogenic period
11.4.4.2 Growth patterns
11.4.4.3 Migration and cell adhesion
11.5 Mechanical mechanisms
11.6 Model systems in which to study cortical folding
11.6.1 Cerebral organoids
11.6.2 Ferret
11.6.3 Nonhuman primates
11.6.4 Human fetal tissue
11.7 Neurodevelopmental disorders
11.7.1 Lissencephaly
11.7.2 Polymicrogyria
11.7.3 Other folding disorders
11.8 Conclusions
Acknowledgments
References
Part II: Generation of neuronal diversity
12 - Cell biology of neuronal progenitor cells
12.1 Introduction
12.2 Location of neuronal progenitors
12.2.1 Multipotent progenitor cells in the ventricular zone generate CNS neurons
12.2.1.1 Neuroepithelial cells
12.2.1.2 Radial glia are neuronal progenitor cells
12.2.2 Neuronal progenitor cells in the subventricular zone
12.2.3 Other non-VZ/SVZ neuronal progenitor cells
12.2.3.1 The dentate gyrus
12.2.3.2 The external granule layer in the cerebellum
12.2.3.3 The retina
12.2.4 The peripheral nervous system
12.2.5 Adult neurogenesis
12.3 Creating different types of neuronal progenitor cells
12.3.1 Neuronal progenitor diversification begins with a regional address
12.3.2 Neuronal progenitor cells are specified temporally
12.3.2.1 Temporal order of neuron generation in the cerebral cortex
12.3.3 Molecular heterogeneity in neuronal progenitor cells
12.4 Cell lineage analysis reveals the fate of individual neuronal progenitor cells
12.4.1 Leading the way: cell lineage analysis in the invertebrate nervous system
12.4.2 Cell lineage analysis in the mammalian nervous system
12.4.3 Lineage analysis, the movie
12.5 Structure and dynamism of neuronal progenitor cells
12.5.1 Interkinetic nuclear migration
12.5.2 Nuclear movement of non-APCs progenitor cells
12.5.3 The structure of radial glia cells
12.5.3.1 Apical-basal processes
12.5.3.2 Adherens junctions
12.5.3.3 Gap junctions
12.5.4 Morphological transitions of neural progenitor cells
12.6 Asymmetric cell division for neuronal diversity
12.6.1 Establishing cell polarity and mitotic spindle orientation
12.6.2 Spindle orientation and cell fate
12.6.3 Asymmetric segregation of the centrosome and the primary cilium membrane
12.6.4 Asymmetric inheritance of the midbody
12.6.5 Asymmetric localization of cell fate determinants
12.7 Progenitor microenvironment and regulating neuronal progenitor number
12.7.1 Fgfs regulate brain size
12.7.2 Shh and cerebellar granule neuron generation
12.7.3 Ξ²-Catenin and Wnt pathway
12.7.4 Apoptosis
12.8 Summary
Acknowledgments
References
13 - Notch and neural development
13.1 History of Notch signaling
13.2 Molecular mechanisms
13.2.1 Notch pathway components
13.2.2 Ligand activation of the Notch receptor
13.2.3 Notch and the balancing act
13.3 Signaling diversity and cis-inhibition
13.4 Timing and feedback are everything
13.5 Notch and the maintenance of neural stem cells during nervous system development
13.6 Notch and the generation of interneuron diversity
13.7 Postnatal neurogenesis and gliogenesis
13.8 Notch, glial cell fate, and maturation
13.9 Notch and neuronal migration
13.10 Notch and dendrite morphogenesis
13.11 Synaptic plasticity and Notch signaling
13.12 Embryonic stem cells and clinical perspectives
13.13 Conclusion
References
14 - bHLH factors in neurogenesis and neuronal subtype specification
14.1 Overview of review content
14.2 Identification of neural bHLH transcription factors: History and evolutionary conservation between fly and mammal
14.2.1 The proneural bHLH factors
14.2.2 The E-proteins: heterodimeric partners for proneural bHLH factors
14.2.3 HES, HEY, and ID bHLH factors: inhibitors of neural differentiation
14.3 bHLH factor function in neuronal differentiation
14.3.1 Interplay between notch and proneural bHLH proteins
14.3.2 Refinements in the models for transition from progenitor to differentiated neuron
14.4 Functions of bHLH transcription factors in neuronal subtype specification
14.5 Molecular characteristics of bHLH transcription factors
14.5.1 Crystal structure of bHLH proteins: DNA recognition and dimer selectivity
14.5.2 Structure function analysis of proneural bHLH proteins
14.6 Protein-Protein interactions modulating cell type-specific functions of neural bHLH factors
14.7 Transcriptional targets of proneural bHLH factors
14.8 Transcriptional regulation of bHLH gene expression
14.9 Posttranslational control of neural bHLH transcription factor function
14.10 Reprogramming activities of proneural bHLH factors
14.11 Perspective
References
15 - The specification and generation of neurons in the ventral spinal cord
15.1 Introduction and general organization
15.2 Induction of spinal cord tissue and initiation of regional pattern
15.2.1 The emergence and organization of cell subtypes in the ventral spinal cord
15.2.2 Shh signaling and ventral cell fate specification
15.2.3 Transcriptional control of progenitor gene expression
15.2.4 Additional signaling influences over progenitor gene expression patterns
15.3 Spinal cord neurogenesis
15.3.1 Control of cell cycle progression and exit in neuronal progenitors
15.3.2 Coordination of cell fate and neurogenesis
15.4 The generation of differentiated neuronal cell subtypes
15.4.1 Motor neuron axial subclass specification: rostral-caudal patterning of the spinal cord influences cell fate within a dorsa ...
15.4.2 Genetic programs in postmitotic cells
15.4.3 Motor neuron subclass diversification
15.4.4 Correlation between cell fate and locomotor circuits
References
16 - Neurogenesis in the cerebellum
16.1 Introduction to the cerebellum
16.2 Overview of cerebellar development
16.3 Establishing the cerebellar territory
16.3.1 Establishing the cerebellar territory along the anterior-posterior axis: the isthmic organizer
16.3.2 Establishing the cerebellar territory along the dorsal-ventral axis
16.4 The cerebellar ventricular zone and its derivatives
16.4.1 Ventricular zone development and neurogenesis in ventricular zone
16.4.2 Molecular mechanisms that regulate the differentiation and migration of Purkinje cells and GABAergic neurons of CN
16.4.3 Molecular mechanisms that regulate development of PWM and GABAergic interneurons
16.5 The cerebellar rhombic lip and its derivatives
16.5.1 Rhombic lip induction and neurogenesis within the rhombic lip
16.5.2 Regulation of granule cell development
16.5.2.1 Regulation of tangential migration of granule neuron precursors from the rhombic lip
16.5.2.2 Regulation of proliferation and differentiation of GNPs in the EGL
16.5.2.3 Regulation of radial migration of granule cells from the EGL to the IGL
16.5.3 Regulation of differentiation and migration of glutamatergic neurons of CN and UBCs
16.6 Cerebellar stem cells and regeneration of the cerebellum
16.7 Conclusions and future perspectives
References
17 - The generation of midbrain dopaminergic neurons
17.1 Introduction
17.1.1 Dopamine
17.1.2 Dopamine system in the brain
17.1.2.1 Midbrain dopamine neurons-anatomically defined groups
17.1.2.2 Midbrain dopamine neurons-groups defined by molecular profiles
17.2 The development of midbrain dopaminergic neurons-general overview
17.3 Generation of midbrain dopaminergic progenitors: patterning, specification, and proliferation
17.3.1 Patterning
17.3.2 Specification and proliferation
17.3.2.1 The role of signaling centers and secreted factors
17.3.2.2 The role of transcription factors
17.3.2.3 Diversity in midbrain dopaminergic progenitors
17.4 Generation of immature and mature midbrain dopaminergic neurons
17.4.1 Regulation of maturation
17.4.2 Migration of midbrain dopaminergic neurons
17.4.3 Axonal pathfinding of midbrain dopaminergic neurons
17.5 The terminal differentiation of the mature dopaminergic neuron
17.6 Maintenance of midbrain dopaminergic neurons
17.7 Perspectives
References
18 - Neurogenesis in the basal ganglia
18.1 Introduction
18.2 Organization of embryonic subdivisions and their relationship to mature structures and cell types
18.2.1 Subdivisions of the mature and embryonic basal ganglia
18.2.2 Cellular organization of the developing basal ganglia
18.2.3 Fate analysis of the GEs and their subdivisions
18.3 Regional specification of subdivisions of the embryonic basal ganglia
18.3.1 Morphogen and growth/differentiation factor signaling in the developing basal ganglia
18.3.1.1 Shh signaling
18.3.1.2 Receptor tyrosine kinase signaling
18.3.1.3 Wnt signaling
18.3.1.4 Tgf-Ξ² signaling
18.3.1.5 Retinoid signaling
18.3.1.6 Notch signaling
18.3.2 Basal ganglia specification
18.3.3 LGE and CGE specification
18.3.4 MGE and POA specification
18.3.5 Septum specification
18.4 Generation of neuronal subtypes
18.4.1 LGE and CGE neuronal derivatives
18.4.1.1 Medium-sized striatal projection neurons
18.4.1.2 Olfactory bulb interneurons
18.4.1.3 Cortical and amygdalar interneurons
18.4.2 MGE and POA neuronal derivatives
18.4.2.1 Globus pallidus projection neurons
18.4.2.2 Striatal interneurons
18.4.2.3 Cortical interneurons
18.4.3 Cis-regulatory elements and epigenetics of basal ganglia development
18.4.4 Engineering basal ganglia neurons in vitro
18.5 Summary
References
19 - Specification of cortical projection neurons: transcriptional mechanisms
19.1 Introduction
19.2 Neocortical progenitors
19.3 Neocortical progenitor cell-fate acquisition and plasticity
19.4 Molecular controls over neocortical projection neuron subtype specification, development, and diversity
19.4.1 Subtype specification of corticofugal projection neurons
19.4.2 Subtype specification of callosal projection neurons
19.4.3 Areal controls over diversity of neocortical projection neuron subtypes
19.5 Progressive restriction and refinement of cortical projection neuron subtypes
19.6 Generation of cortical projection neuron subtypes in vitro from human pluripotent stem cells
19.7 Subtype-specific circuit wiring by growth cones
19.8 Conclusions
References
20 - The generation of cortical interneurons
20.1 Diversity of mature cortical interneurons
20.1.1 Parvalbumin interneurons
20.1.2 Somatostatin interneurons
20.1.3 Vasoactive intestinal peptide interneurons
20.1.4 Lamp5 interneurons
20.1.5 Gamma-synuclein and Serpinf1 interneurons
20.2 Developmental origin of cortical interneurons
20.2.1 The ventral origin of cortical neurons
20.2.2 Genetic determinants involved in the specification of the MGE and CGE
20.2.3 Place and time of origins of cortical interneurons
20.2.4 Fate mapping strategies to assess the origin of cortical interneurons
20.2.5 Genetic programs underlying the developmental emergence of interneurons
20.3 Migration of cortical interneurons
20.3.1 The influence of non-cell-autonomous signals on interneurons development
20.4 Postnatal cortical interneuron development
20.4.1 GABA is depolarizing during development
20.4.2 Early patterns of network activity
20.4.3 Role of activity in interneuron development
20.4.4 Interneuron development and neurological disorders
Acknowledgments
References
21 - Specification of retinal cell types
21.1 Introduction
21.2 Retinal progenitor cell competence
21.2.1 Establishment of retinal neuron and MΓΌller glia birth order
21.2.2 Clonal analyses in the developing retina
21.2.3 Intrinsic versus extrinsic control of neurogenesis in the mammalian retina
21.3 Intrinsic regulation of retinal development
21.3.1 Early eye formation
21.3.2 Retinal neurogenesis
21.3.3 Intrinsic factor regulation of RGC development
21.3.4 Intrinsic factors regulating photoreceptor development
21.3.5 Epigenetic control of retinogenesis
21.3.6 MicroRNA-mediated regulation of retinal genes
21.4 Extrinsic regulation of retinogenesis
21.4.1 Bmp/TgfΞ² superfamily signaling
21.4.2 Fgf signaling
21.4.3 Notch signaling
21.4.4 Retinoic acid signaling
21.4.5 Hh signaling
21.4.6 Wnt/Ξ²-catenin signaling
21.5 Regenerative capacity of the retina
21.6 Perspective
Glossary
References
22 - Neurogenesis in the postnatal V-SVZ and the origin of interneuron diversity
22.1 Newborn neurons are generated in the V-SVZ of the adult brain
22.2 Identification and origin of adult neural stem cells
22.3 OB interneurons are heterogeneous
22.4 Spatial specification of OB interneuron identity
22.5 Temporal regulation of OB interneuron production
22.6 Conclusion
Acknowledgments
References
23 - Neurogenesis in the damaged mammalian brain
23.1 Introduction
23.2 Persistent versus injury-induced neurogenesis in the adult brain
23.2.1 Neurogenesis in the intact brain
23.2.1.1 Active neurogenic regions
23.2.1.2 Common and distinct features of adult neurogenic niches
23.2.1.3 Cryptic or less active neurogenic regions
23.3 Neurogenesis in the injured brain
23.3.1 Stimulation of ongoing neurogenesis after damage
23.3.2 Ectopic production of new neurons and glia in damaged brains
23.3.2.1 Acute central nervous system injury
23.3.2.1.1 Neocortex
23.3.2.1.2 Striatum
23.3.2.1.3 Hippocampus
23.3.2.1.4 Substantia nigra
23.3.2.1.5 Spinal cord
23.3.2.1.6 Retina
23.3.2.1.7 Other regions of the central nervous system
23.3.2.2 Neurogenesis in chronic neurodegenerative conditions
23.3.2.2.1 Alzheimer's disease
23.3.2.2.2 Huntington disease
23.3.2.2.3 Other neurodegenerative disorders
23.4 Identity, integration, and extent of regeneration of new neurons
23.4.1 Neocortex and hippocampus
23.4.2 Striatum
23.4.3 Other regions of the central nervous system
23.5 Contribution of injury-induced neurogenesis to functional recovery
23.5.1 Attenuation of neurogenesis
23.5.2 Enhancement of neurogenesis
23.5.3 Just a correlation or the cause?
23.6 How widespread is injury-induced neurogenesis?: technical issues
23.7 Cellular origins of injury-induced neurogenesis
23.7.1 Contribution of NPCs in known neurogenic niches
23.7.2 Identity of cells that generate new neurons
23.7.3 Possible cellular sources outside neurogenic niches
23.8 Gliogenesis after injury
23.8.1 Oligodendrogenesis
23.8.2 Astrogenesis
23.9 Mechanisms underlying injury-induced neurogenesis
23.9.1 Cell-intrinsic limitation of NPCs
23.9.1.1 Limited number and expansion of NPCs
23.9.1.2 Limited plasticity of NPCs
23.9.1.3 Intrinsic fate determinants of NPCs
23.9.1.3.1 Maintenance and proliferation of NSCs
23.9.1.3.2 Differentiation of NSCs
23.9.1.3.3 Neuronal subtype specification
23.9.2 Environmental restrictions
23.9.2.1 Growth factors
23.9.2.2 Differentiation factors
23.9.2.3 Migratory cues
23.9.2.4 Survival and maturation signals
23.9.2.5 Inflammatory and immune signals
23.9.2.6 Neurotransmitter signals
23.9.2.6.1 Glutamate and GABA
23.9.2.6.2 Dopamine
23.9.2.6.3 Serotonin
23.9.2.6.4 Neuropeptides and other neurotransmitters
23.9.2.6.5 Specific neuronal populations
23.9.2.7 Hormones
23.9.2.8 Other signals
23.9.2.8.1 Nitric oxide
23.9.2.8.2 Lipid mediators
23.9.2.8.3 Cell grafts
23.10 Neuronal cell reprogramming
23.11 Link between neurodegeneration and neurogenesis
23.12 Neurovascular niche
23.13 Nonneurogenic roles of adult NPCs in brain repair
23.14 Future perspectives
Acknowledgments
References
24 - Neuronal identity specification in the nematode Caenorhabditis elegans
24.1 Introduction
24.2 Neuron classification
24.3 Neuronal cell lineages
24.4 Genes controlling lineage decisions
24.4.1 Neuronal versus nonneuronal lineage transformations
24.4.2 Neuron lineage alterations and losses
24.5 Terminal selectors control neuron class specification
24.6 Genes controlling neuron subclass diversification
24.6.1 Diversifying motor neuron classes
24.6.2 Neuronal identity diversification across the left/right axis
24.7 Other regulatory routines operating during neuronal differentiation
24.8 Linking neuronal class specification to lineage
24.9 Concluding remarks
Acknowledgments
References
25 - Development of the Drosophila melanogaster embryonic CNS: from neuroectoderm to unique neurons and glia
25.1 Introduction
25.2 Patterning of the neuroectoderm: breaking the homogeneity
25.2.1 Patterning the ventral neuroectoderm
25.2.2 Patterning the brain neuroectoderm
25.3 Homologous neuromeres: same but different
25.4 The chosen one: lateral inhibition
25.4.1 Delamination of VNC neuroblasts
25.4.2 Delamination of brain neuroblasts
25.5 Unequal legacy: asymmetric cell division
25.6 One thing at a time: the temporal cascade
25.7 Regulation of neuroblast and daughter cell proliferation
25.7.1 NB cell cycle exit and daughter cell proliferation switches: the role of cell cycle genes
25.7.2 NB cell cycle exit and daughter cell proliferation switches: the role of late temporal and Hox genes
25.7.3 NB exit and daughter cell proliferation switches: the role of the Notch pathway
25.7.4 NB exit and daughter cell proliferation switches: the role of early temporal and pan-neural genes
25.7.5 Brain-specific NB behavior: type II NBs
25.7.6 Brain-specific NB behavior: mushroom body and IPC NBs
25.8 The role of programmed cell death in the Drosophila embryonic VNC
25.9 Finishing the picture: specification of unique cell types
25.9.1 Specifying brain cells
25.9.2 Specifying VNC neuropeptide cells
25.9.3 Specifying motor neurons
25.9.4 Specifying midline neurons
25.9.5 Specifying glia cells
25.9.5.1 Specifying lateral glia cells
25.9.5.2 Specifying midline glia cells
25.10 Conclusions
25.11 Outstanding issues
Acknowledgments
References
26 - Neurogenesis in zebrafish
26.1 Neural plate induction and patterning
26.1.1 Formation of the neural tube
26.1.2 Neural plate induction
26.1.3 Neural plate patterning along the anteroposterior axis
26.2 Establishment of the primary neuronal scaffold
26.2.1 Organization of the primary neuronal scaffold
26.2.2 Formation of the primary neuronal scaffold
26.2.2.1 Identification of competent proneural domains within the neural plate
26.2.2.2 Neurogenesis control within the proneural clusters
26.2.2.2.1 Lateral inhibition in Drosophila
26.2.2.2.2 Lateral inhibition in vertebrates
26.2.2.2.3 Regulation of notch signaling
26.2.2.3 Determination of primary neuronal identities
26.2.2.3.1 Morphogens
26.2.2.3.2 Notch signaling
26.3 Secondary neurogenesis
26.3.1 Functional anatomy of secondary neurogenesis
26.3.1.1 Motor and sensory systems
26.3.1.2 Neuromodulatory, neurohormone, and neuropeptide systems
26.3.2 Molecular and cellular mechanisms of secondary neurogenesis
26.3.2.1 Secondary neurogenesis: balance between proliferation and differentiation
26.3.2.2 Neuroblast migration
26.3.2.2.1 Facial branchiomotor neurons migration
26.3.2.2.2 Migration of precursor cells in the cerebellum
26.3.2.3 Neuronal subtype specification
26.3.2.3.1 Specification of subtypes in the spinal cord
26.3.2.3.2 Neuromodulatory systems
26.3.2.3.2.1 DA neurons
26.3.2.3.2.2 NA neurons
26.3.2.3.2.3 5-HT and HA neurons
26.3.2.3.2.4 Diencephalic/hypothalamic neurohormones and neuropeptides
26.4 Adult neurogenesis and plasticity
26.4.1 Anatomy of adult neurogenesis
26.4.1.1 Neurogenesis domains
26.4.1.2 Influence of physiological parameters on neurogenic activity
26.4.2 Molecular and cellular mechanisms of adult neurogenesis
26.4.2.1 Localization, identity, and properties of adult progenitor cells
26.4.2.1.1 NSCs in the adult telencephalon: markers and lineages
26.4.2.1.1.1 Continuous lineages from embryo to adult contribute to generate an ordered'' pallial structure
26.4.2.1.1.2 Changes in neurogenesis with aging
26.4.2.1.2 NSCs at the adult MHB: markers and lineages
26.4.2.1.3 NSCs in the adult cerebellum: markers, lineage
26.4.2.2 Molecular pathways of adult neural progenitor maintenance and recruitment
26.4.2.2.1 Notch
26.4.2.2.2 microRNA-9
26.4.2.2.3 Fezf2
26.4.2.2.4 Fgf
26.4.2.2.5 Steroids
26.4.2.2.6 BDNF
26.4.2.2.7 Id (inhibitor of DNA binding)
26.4.2.3 Adult neurogenesis and plasticity upon brain or spinal injury
26.4.2.3.1 Neurogenesis and regeneration in the telencephalon
26.4.2.3.2 Neurogenesis and regeneration in the diencephalon (DA neurons)
26.4.2.3.3 Neurogenesis and regeneration in the optic tectum
26.4.2.3.4 Neurogenesis and regeneration in the cerebellum
26.4.2.3.5 Neurogenesis and regeneration in the spinal cord
References
27 - Gene regulatory networks controlling neuronal development: enhancers, epigenetics, and functional RNA
27.1 Introduction-genomic control of cell identity in the brain
27.2 Overview of gene regulation and the control of neuronal diversity
27.3 Interactions between transcription factors, regulatory DNA, and epigenetics
27.4 Enhancers
27.4.1 Mapping and functional prediction of enhancers in the brain
27.4.2 Enhancer activity in brain development
27.4.3 Combinatorial enhancer binding of transcription factors activates or represses
27.4.4 Comparative genomics-evolutionary conservation and novelty of brain enhancers
27.4.5 Example: ARX expression is regulated by coordinated activity of distal enhancers
27.4.6 Role of enhancer variation in neurodevelopmental and psychiatric disorders
27.4.7 Current questions regarding enhancer function
27.5 Epigenetics
27.5.1 How chromatin state contributes to gene regulation
27.5.2 Functional genome annotation
27.5.2.1 DNA methylation
27.5.2.2 Histone modification
27.5.2.3 Chromatin accessibility
27.5.3 Lineage specification and chromatin in the brain
27.5.4 Interaction between transcription factors and chromatin
27.5.5 Role of chromatin remodelers in neurodevelopmental disorders
27.5.6 Current questions regarding epigenetics
27.6 Regulatory RNA in brain development
27.6.1 Functional RNA: miRNA, lncRNA, eRNA
27.6.2 miRNA: a brief overview
27.6.3 lncRNA-evidence for function
27.6.4 eRNA-transcriptional artifacts or functional molecules?
27.6.5 Current questions regarding functional RNA
27.7 Putting it all together-gene regulatory networks
27.7.1 Example: Nkx2-1 in the basal ganglia
27.8 Conclusion
References
28 - Posttranscriptional and translational control of neurogenesis: roles for RNA-binding proteins
28.1 Introduction
28.1.1 Neurogenesis
28.1.2 Posttranscriptional regulation
28.2 Alternative splicing
28.2.1 Global and dynamic splicing patterns
28.2.2 Trans-regulators of splicing
28.2.3 Summary I
28.3 From nucleus to cytoplasm
28.3.1 The exon junction complex
28.3.2 Nonsense-mediated decay
28.3.3 Summary II
28.4 Translational control
28.4.1 Core translational machinery
28.4.2 The elavl family members
28.4.3 RNA localization, transport, and translation
28.4.4 Summary III
28.5 The epitranscriptome
28.5.1 Readers and writers
28.5.2 Summary IV
28.6 Perspectives
References
29 - Human neurogenesis: single-cell sequencing and in vitro modeling
29.1 Introduction
29.2 Single-cell sequencing modalities
29.2.1 Whole-cell RNA-sequencing to identify molecular signatures of known and novel cell types
29.2.2 Nuclei sequencing to discover novel human cell types
29.2.3 Multimodal integration of transcriptomic, morphologic, and physiologic features highlights functional significance of cellu ...
29.2.4 ATAC-seq, methylation, and other measures of chromatin state
29.2.5 Other modalities
29.2.6 In situ sequencing and other imaging strategies
29.3 Overview of analytical approaches and strategies
29.3.1 Clustering and basic analysis strategies
29.3.2 Approaches to lineage reconstruction
29.3.2.1 In vitro modeling of human neurogenesis
29.4 Cell culture strategies
29.4.1 Stem cells and reprogramming
29.4.2 Adherent culture systems
29.4.3 Brain organoid models
29.5 Modeling development in organoids
29.5.1 Regionalization
29.5.2 Timing of maturation compared to normal development
29.5.3 Developmental trajectories and neuronal differentiation
29.5.4 Cellular diversity
29.5.5 Architectonics
29.5.6 Cellular dynamics and migration
29.5.7 Reproducibility
29.6 Regional interactions
29.6.1 Whole brain organoids
29.6.2 Organoid fusing
29.7 Functional activity
29.7.1 Modeling circuits
29.7.2 Single-cell analysis of in vitro cerebral organoid models
29.7.3 Organoid models to study human evolution
29.8 Disease phenotypes
29.9 Engineering organoids
29.10 Conclusion
References
Part III: Development of glia, blood vessels, choroid plexus, immune cells in the nervous system
30 - A golden age for glial biology
30.1 Overview
30.2 Brief summary of section chapters
30.2.1 Chapters 31-33: neural stem cells and astrocytes
30.2.2 Chapters 34-40: myelinating cells
30.2.3 Chapters 41-43: microglia, ependyma, perivascular cells, and meninges
30.3 Conclusion
31 - Neural stem cells among glia
31.1 Introduction
31.2 NSCs among glia in the developing brain
31.2.1 Neuroepithelial cells
31.2.2 Radial glia
31.2.3 Intermediate (basal) progenitor cells
31.2.4 Outer radial glia
31.3 Molecular regulation of progenitor proliferation, cell fate, and polarity
31.3.1 Mapping progenitor cell fates
31.3.2 Role of apical-basal polarity in progenitors
31.3.2.1 Regulation at the apical surface
31.3.2.2 Role of the basal process
31.3.3 New models of molecular regulation in progenitors
31.4 NSCs among glia in the postnatal brain
31.4.1 RG persist after birth and function as NSCs in some vertebrates
31.4.2 NSCs (Type B1 cells) in the adult mammalian V-SVZ
31.4.3 NSCs (radial astrocytes) in the adult hippocampus
31.4.4 Regulation of adult NSCs
31.5 Link between embryonic and adult glial cells that function as NSCs
31.6 Origin of oligodendrocytes from RG and adult V-SVZ astrocytes
31.7 Evolutionary perspective
31.8 Perspective for brain repair
31.9 Conclusion
Acknowledgments
References
32 - Mechanisms of astrocyte development
32.1 Introduction
32.1.1 Overview of astrocyte function in the central nervous system
32.1.2 Why is the study of astrocytes uniquely challenging?
32.1.2.1 Interspecies differences in astrocyte developmental lineages
32.1.2.2 The absence of a clear developmental endpoint
32.1.2.3 The lack of molecular tools
32.1.3 Overview of the chapter
32.2 The origins of astrocytes
32.2.1 Use of in vitro culture methods to generate astrocytes
32.2.2 Use of induced pluripotent stem cell technology to generate astrocytes in vitro
32.2.3 Molecular mechanisms of astrocyte specification and initiation
32.2.3.1 1996-99: Role of signaling molecules
32.2.3.2 1996-99: Suppression of astrocyte fate and epigenetic states
32.2.3.3 2000-04: Discovery of the role of Notch signaling to promote astrocytes
32.2.3.4 2005: Feedback mechanisms controlling astrocyte fate
32.2.3.5 2006: Discovery of NFIA, which controls the neuron-glia switch
32.2.3.5.1 2009: NFIA also promotes differentiation of astrocytes, after the neuron-glia switch
32.2.3.5.2 2012: Relationship of NFIA with transcription factor Sox9
32.2.3.5.3 2014: Relationship of NFIA with transcription factors Sox10 and Olig2 to control oligodendrocyte fate
32.2.3.6 2006-present: discoveries of other pathways, transcription factors, and mechanisms of astrocyte fate determination
32.2.3.6.1 Receptors and signaling pathways: ErbB4 and MEK/ERK pathway
32.2.3.6.2 Transcription factors: Coup-TFI, Lhx2, and Zbtb20
32.2.3.6.3 Epigenetic controls: Hdac3 in the astrocyte-oligodendrocyte fate decision and the role of chromatin loops
32.2.4 Patterning of the neural tube and astrocytes
32.2.4.1 Are astrocytes patterned?
32.2.4.2 Patterning as a mechanism to generate astrocyte diversity
32.3 Mechanisms of astrocyte differentiation
32.3.1 The search for stage-specific and subtype-specific pan-astrocytic markers
32.3.1.1 Classical markers of astrocytes
32.3.1.2 Newly identified transcription factors as astrocyte markers
32.3.1.3 Functional proteins as mature astrocyte markers
32.3.1.4 Emerging astrocyte markers based on transcriptional profiling
32.3.2 Defining the intermediate phases of astrocyte lineage trajectory
32.3.2.1 Directionality of astrocyte migration from the subventricular zone
32.3.2.2 Location of astrocyte precursor proliferation
32.3.2.3 Molecular regulation of the intermediate phases of astrocyte development
32.4 Morphologic and functional maturation of astrocytes
32.4.1 Morphologic maturation of astrocytes
32.4.2 Functional maturation of astrocytes
32.4.2.1 Lessons from the fly about neuron-glia interactions
32.4.2.2 Neuronal activity sculpts astrocyte maturation
32.5 The development of astrocyte diversity
32.5.1 Morphological diversity across the adult central nervous system
32.5.2 Regional and functional diversity across the adult central nervous system
32.5.3 Does regional diversity control function of spatially separated astrocytes?
32.5.4 Local diversity at specific regions and their contribution to astrocyte function
32.5.5 Other aspects of astrocyte diversity
32.6 Conclusions and future directions
References
33 - Astrocyte-neuron interactions in synaptic development
33.1 Developmental stages of synapse formation and maturation
33.2 Role of astrocytes in synaptic development
33.2.1 Contact-mediated astrocyte synaptogenic signals
33.2.1.1 Integrin-protein kinase C
33.2.1.2 Neurexin
33.2.1.3 Gamma protocadherins
33.2.1.4 Neuroligins
33.2.1.5 Eph/ephrin
33.2.2 Astrocyte-secreted synapse-regulating signals
33.2.2.1 Synapse number
33.2.2.1.1 Thrombospondin
33.2.2.1.2 Sparcl1
33.2.2.1.3 Transforming growth factor beta
33.2.2.2 Presynaptic function
33.2.2.2.1 Cholesterol and lipid metabolism
33.2.2.3 Postsynaptic function
33.2.2.3.1 Glypicans
33.2.2.4 Tumor necrosis factor alpha
33.2.2.4.1 Chordin-like 1
33.2.2.4.2 Chondroitin sulfate proteoglycans
33.2.2.5 Negative synaptic regulators
33.2.2.5.1 SPARC
33.2.2.6 Additional astrocyte-derived signals
33.2.2.7 Inhibitory synapses
33.2.3 Astrocyte elimination of synapses
33.3 Region, temporal, and neuronal regulation of astrocyte synaptogenic cues
33.3.1 Regional heterogeneity of astrocyte synaptogenic gene expression
33.3.2 Temporal changes in astrocyte synaptogenic gene expression
33.3.3 Neuronal regulation of synaptogenic cue expression in astrocytes
33.4 Conclusion
References
34 - Specification of oligodendrocytes
34.1 Introduction
34.2 Determinants of oligodendroglial fate
34.3 Determinants of oligodendroglial identity
34.4 Determinants of progenitor state maintenance
34.5 Determinants of progression from the progenitor state
34.6 Determinants of terminal differentiation and the fully differentiated state
34.7 Concluding remarks perspectives
References
35 - Signaling pathways that regulate glial development and early migration-oligodendrocytes
35.1 Introduction
35.2 Signaling pathways regulating the initial appearance of oligodendrocyte precursors
35.2.1 Timing and localization of appearance of OPCs
35.2.2 Molecular control of early OPC appearance
35.2.2.1 Sonic hedgehog
35.2.2.2 Bone morphogenetic proteins
35.2.2.3 Wnts
35.2.2.4 Neuregulin
35.2.2.5 FGF
35.3 Regulation of OPC migration
35.3.1 Mechanisms of OPC dispersal: engagement of the vasculature
35.3.2 Molecular guidance of OPC dispersal
35.3.2.1 Netrins
35.3.2.2 Semaphorins
35.3.3 Molecular control of OPC motility
35.3.3.1 Growth factors
35.3.3.2 Neurotransmitters and channels
35.3.3.3 Chemokines
35.3.4 Signals regulating the final localization of oligodendrocytes
35.3.4.1 CXCL1
35.3.4.2 Tenascin C
35.4 Regulation of OPC differentiation
35.4.1 Cell extrinsic regulation of oligodendrocyte differentiation
35.4.1.1 LINGO-1
35.4.1.2 PSA-NCAM
35.4.1.3 Notch/delta
35.4.2 Cell-intrinsic regulators of oligodendrocyte differentiation
35.4.3 Transcriptional regulators of OPC terminal differentiation
35.4.3.1 Negative transcriptional regulators of OPC terminal differentiation
35.4.3.2 Positive regulators of OPC terminal differentiation
35.4.3.3 Intrinsic transcriptional regulation of oligodendrocyte maturation and myelination
35.5 Epigenetic regulation of oligodendrocyte development
35.5.1 ATP-dependent chromatin remodelers
35.5.2 Histone-modifying enzymes
35.5.3 miRNAs in oligodendrocyte development
35.5.4 lncRNAs in oligodendrocyte development
35.6 Conclusions
References
36 - Neuron-glial interactions and neurotransmitter signaling to cells of the oligodendrocyte lineage
36.1 Introduction
36.2 Distinguishing characteristics of OPCs, premyelinating oligodendrocytes, and mature oligodendrocytes
36.2.1 OPC distribution, morphology, and proliferation
36.2.2 Distribution and morphology of premyelinating oligodendrocytes and oligodendrocytes
36.2.3 Physiological properties of oligodendrocyte lineage cells
36.2.4 Transcriptional expression profiles across the oligodendrocyte lineage
36.3 Neurotransmitter signaling within the oligodendrocyte lineage: glutamate
36.3.1 AMPA receptor signaling within oligodendrocyte lineage cells
36.3.2 NMDA receptor signaling within oligodendrocyte lineage cells
36.3.3 Metabotropic glutamate receptors within oligodendrocyte lineage cells
36.3.4 Glutamate receptor expression during progenitor differentiation
36.4 Neurotransmitter signaling within the oligodendrocyte lineage: GABA, acetylcholine, and ATP
36.5 Synaptic signaling between neurons and OPCs
36.5.1 A surprising discovery: evidence for the existence of neuron-OPC synapses
36.5.2 Do neuron-OPC synapses regulate oligodendrogenesis?
36.5.3 Activity-dependent myelination
36.5.4 Additional features of neuron-OPC synapses: signaling functions beyond oligodendrogenesis?
36.6 Oligodendrocyte lineage cells in the context of disease and injury
36.6.1 OPC reactivity and vulnerability of oligodendrocyte lineage cells to pathology
36.6.2 Perinatal hypoxia and ischemia
36.6.3 OPCs and hypomyelination/demyelination
36.6.4 Tumorigenesis and gliomas
36.7 Conclusions/future directions
References
37 - Nonmammalian model systems of zebrafish
37.1 History and attributes of the zebrafish model system
37.1.1 Establishment of a new animal model
37.1.2 The zebrafish toolbox
37.2 Zebrafish glial classification
37.3 Zebrafish oligodendrocyte development
37.3.1 Oligodendrocyte specification
37.3.2 Oligodendrocyte lineage cell migration, proliferation, and differentiation
37.4 Zebrafish peripheral glia
37.4.1 Schwann cells and the zebrafish lateral line system
37.4.2 Genetic control of peripheral glial development
37.4.3 Motor root perineurial cells originate as CNS glia
37.4.4 Glial cell interactions at the CNS-PNS interface
37.5 Zebrafish radial glia
37.6 Zebrafish microglia
37.7 Conclusion
References
38 - Specification of macroglia by transcription factors: Schwann cells
38.1 Introduction
38.2 Specification of Schwann cells from neural crest
38.2.1 Alternate developmental fates of Schwann cell precursors
38.3 Immature Schwann cells: radial sorting and transition to myelination
38.4 Signaling pathways regulating the myelin program
38.4.1 Neuregulin
38.4.2 G protein-coupled receptor 126 signaling
38.4.3 Mitogen-activated protein kinase signaling. ERK1/2
38.4.4 PI-3 kinase and mTOR signaling
38.4.5 Calcium and prostaglandin signaling converging on nuclear factor of activated T-cell (NFAT) transcription factors in Schwan ...
38.4.6 Negative regulators of myelination
38.5 Integration of signaling pathways at myelin genes
38.6 Epigenetic regulation of Schwann cell differentiation
38.7 Reprogramming Schwann cell behavior in pathology
38.8 Conclusion
List of acronyms and abbreviations
References
39 - Signaling pathways that regulate glial development and early migration-Schwann cells
39.1 Introduction
39.1 Overview of Schwann cell development
39.1.1 Schwann cell precursors, the glial cells of early embryonic nerves
39.1.2 Immature Schwann cells
39.1.3 Axonal signals
39.1.4 Boundary cap cells
39.2 Developmental potential and Schwann cell plasticity
39.3 Major differences among migrating neural crest cells, SCP, and iSch
39.4 Gliogenesis from crest cells: the appearance of SCP
39.4.1 HDAC1/2
39.4.2 Sox10
39.4.3 NRG1
39.4.4 Notch
39.5 NRG1 and Notch signaling IN SCP
39.5.1 Survival
39.5.2 Migration
39.5.3 NRG1 on developing axons
39.5.4 NRG1 and Notch interact to promote SCP survival and iSch generation
39.6 Schwann cell generation and the architectural reorganization of peripheral nerves
39.7 SCP and early Schwann cells control neuronal survival, nerve fasciculation, and synapse formation
39.7.1 Neuronal survival
39.7.2 Fasciculation and synapse formation
39.8 Schwann cells in late embryonic and perinatal nerves
39.9 Signals that drive Schwann cell proliferation in vivo
39.9.1 Notch
39.9.2 TGFΞ²
39.9.3 YAP/TAZ pathway
39.9.4 NRG1
39.9.5 Laminin and GPR126
39.10 Signals that promote Schwann cell death and survival in vivo
39.11 Radial sorting
39.11.1 Laminin and integrins
39.11.2 NRG1
39.11.3 Lgi4
39.11.4 GPR126
39.11.5 Sox10
39.11.6 HDAC1/2
39.11.7 Zeb2
39.11.8 The HIPPO pathway
39.11.9 Jab 1
39.11.10 Wnt/beta-catenin signaling
39.12 The onset of myelination
39.12.1 Positive regulators
39.12.2 The onset of myelination: negative regulators
39.13 Conclusions
Acknowledgments
References
40 - Structure and function of myelinated axons
40.1 Introduction
40.2 Evolution of the myelinated axon
40.2.1 Ion channel clustering in the axon
40.2.2 Myelin-enablingwrap-id'' advances in cognition
40.3 Myelinating glial cells and axoglial interactions
40.4 Nodes of Ranvier: structure, composition, and function
40.4.1 Nodes of Ranvier
40.4.2 Paranodal junctions
40.4.3 Juxtaparanodes
40.5 Assembly of nodes of Ranvier
40.5.1 Clustering of Na+ channels at nodes of Ranvier in the PNS
40.5.2 Clustering of Na+ channels at nodes of Ranvier in the CNS
40.6 Long-term maintenance of nodes in the PNS and CNS
40.7 Function of nodes in AP propagation and initiation
40.7.1 Developmental maturation of Na+ channel complexes at nodes of Ranvier
40.7.2 Nodal spacing contributes to neuronal computations
40.7.3 Proximal nodes of Ranvier in determining neuronal firing patterns
40.8 Nodes of Ranvier in nervous system disease and injury
40.8.1 Autoimmune disorders
40.8.2 Developmental neuropsychiatric disorders
40.9 Conclusions and outlook
References
41 - Microglia
41.1 Introduction
41.2 Origin and maintenance of microglia
41.2.1 Developmental origins of microglia
41.2.2 Microglia in different species
41.2.3 Microglia turnover in the adult brain
41.3 Microglia as dynamic cells in the CNS
41.3.1 Challenging the term ``resting'' microglia in the healthy CNS
41.3.2 Microglial responses to localized trauma in vivo
41.4 Microglial activation
41.5 Microglial interactions with other cell types
41.6 Microglia and disease
41.6.1 Microglia in multiple sclerosis
41.6.2 Microglia in stroke
41.6.3 Microglia in Alzheimer's disease
41.6.4 Microglia in neuropathic pain
41.6.5 Single-cell approaches to understand microglia heterogeneity
41.7 Concluding remarks
List of abbreviations
References
42 - Ependyma
42.1 Introduction
42.2 Structure of cells in contact with the ventricles
42.2.1 Structure of multiciliated ependymal cells
42.2.1.1 Structure of tanycytes
42.2.1.2 Structure of other cells in contact with ventricles
42.2.2 Origin and developmental mechanisms
42.2.2.1 Ependymal cell specification
42.2.2.2 Ependymal cell differentiation
42.2.2.3 Ependymal cell maturation
42.2.3 Functions in the brain
42.2.3.1 Ependymal epithelium: interface between brain and CSF
42.2.3.1.1 The ependymal junctions
42.2.3.1.2 A filter for brain-CSF exchange
42.2.3.1.3 A regulator of osmotic pressure
42.2.3.1.4 A barrier against harmful substances
42.2.3.1.5 A regulator of peptide concentrations
42.2.3.2 Trophic and metabolic support by ependymal cells
42.2.3.3 Can ependymal cells function as neural stem cells?
42.2.4 Associated pathologies
42.2.4.1 Ependymoma
42.2.4.2 Hydrocephalus
42.3 Summary
References
43 - Meninges and vasculature
43.1 Meninges in development
43.1.1 Meninges assembly to adult structure: histology and molecular signaling
43.1.1.1 Emergence and maturation of the meningeal fibroblast layers
43.1.1.2 Developmental timeline and function of nonfibroblast cells of the meninges
43.1.2 Meninges-brain interface: signals from the meninges regulate development of the CNS
43.1.2.1 Meningeal Cxcl12 in fore- and hindbrain development
43.1.2.2 Meningeal retinoic acid in forebrain and hindbrain development
43.1.2.3 Meningeal bone morphogenic proteins in forebrain development
43.1.2.4 Meningeal deposition and maintenance of the pial BM
43.1.3 Perspectives on the meninges as an interface between the immune system and the brain
43.2 Development of the CNS vasculature
43.2.1 Timing and molecular mechanisms of CNS angiogenesis
43.2.1.1 Developmental timing of CNS vascularization
43.2.1.2 VEGF ligands regulate CNS vascular growth and patterning
43.2.1.3 Endothelial Wnt-Ξ²-catenin signaling is CNS vascular development
43.2.1.4 Integrin Ξ±vΞ²8 in CNS vascular development
43.2.1.5 Retinoic acid in cerebrovascular development
43.2.2 Establishment of the BBB
43.2.2.1 Developmental timing of BBB emergence
43.2.2.2 Molecular control of BBB development
43.2.2.3 Mural cells in regulation of vascular development and BBB maturation
43.2.3 Vascular contribution to neurodevelopmental events
43.2.3.1 Vascular regulation of neuro- and oligodendrogenesis
43.2.3.2 The embryonic vasculature as a migratory scaffold in the forebrain
43.2.3.3 The brain vasculature shapes axonal architecture
43.2.4 hiPSC-based BBB culture models: lessons from CNS vascular development
43.2.5 Summary and conclusions
References
Index
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Y
Z
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