Effects of epidermal growth factor (EGF), transforming growth factor-α (TGFα), and 2,3,7,8-tetrachlorodibenzo-p-dioxin on fusion of embryonic palates in serum-free organ culture using wild-type, EGF knockout, and TGFα knockout mouse strains
✍ Scribed by Barbara D. Abbott; Angela R. Buckalew; Korin E. Leffler
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 152 KB
- Volume
- 73
- Category
- Article
- ISSN
- 1542-0752
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
BACKGROUND
2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) is teratogenic in mice, producing cleft palate (CP). TCDD exposure disrupts expression of epidermal growth factor (EGF) receptor, EGF, and transforming growth factor‐α (TGFα) in the palate and affects proliferation and differentiation of medial epithelial cells. EGF knockout embryos are less susceptible to the induction of CP by TCDD. This study used palate organ culture to examine the hypothesis that EGF enables a response to TCDD.
METHODS
The midfacial tissues from wild‐type (WT), EGF knockout, C57BL/6J, and TGFα knockout embryos were placed in organ culture on gestational day (GD) 12. Palatal explants were cultured for 4 days in serum‐free Bigger's (BGJ) medium with 0.1% dimethyl sulfoxide (DMSO) or 1 × 10^−8^ M TCDD with or without 2 ng of EGF/ml, 1 or 2 ng of TGFα/ml. Effects on palatal fusion were evaluated on day 4 of culture. EGF levels in explants and medium were determined using Luminex technology.
RESULTS
In serum‐free, control medium, palates from all of the strains fused. EGF knockout palates cultured with TCDD (no EGF) fused, but those cultured with TCDD + 2 ng of EGF/ml failed to fuse (p < 0.05 vs. control or TCDD without EGF). TGFα knockout palates failed to fuse when cultured with TCDD + 2 ng of TGFα/ml. EGF levels increased in tissue and accumulated in the medium after 24 hr of culture.
CONCLUSIONS
This study demonstrated that providing EGF to the palates of EGF knockout mice restored the response to TCDD. These studies support the hypothesis that the mechanism for induction of CP by TCDD is mediated via the EGFR pathway. Birth Defects Research (Part A), 2005. Published 2005 Wiley‐Liss, Inc.