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Developmental regulation of the serotonergic transmitter phenotype in rostral and caudal raphe neurons by transforming growth factor-βs

✍ Scribed by Dagmar Galter; Martina Böttner; Klaus Unsicker


Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
195 KB
Volume
56
Category
Article
ISSN
0360-4012

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✦ Synopsis


Serotonergic (5-HT) neurons of the CNS develop as two separate clusters, a rostral and a caudal group, within the brain stem raphe. We show here that the transforming growth factors -␤2 and -␤3 (TGF-␤) and the TGF-␤ type II receptor are expressed in the embryonic rat raphe, when 5-HT neurons develop and differentiate. To investigate putative roles of TGF-␤s in the regulation of 5-HT neuron development we have generated serum-free cultures isolated either from the rostral or the caudal embryonic rat raphe, respectively. In cultures from the caudal E14 raphe saturating concentrations (5 ng/ml) of TGF-␤2 and -␤3 augmented numbers of tryptophan hydroxylase (TpOH) -immunoreactive neurons and cells specifically taking up 5,7-dihydroxytryptamine (5,7-DHT) by about 1.7-fold over a period of 4 days. Treatment with TGF-␤s also increased uptake of 3 H-5HT uptake about 1.7-fold. Alterations in 5-HT neuron numbers were due to the induction of serotonergic markers rather than increased survival, as shown by the efficacy of delayed short-term treatments. Comparing rostral and caudal raphe cultures from different embryonic ages suggests that distinct effects of TGF-␤s reflect the responsiveness of 5-HT neurons at different ages rather than of different origins.