THE DISTRIBUTION OF EPIDERMAL GROWTH-FACTOR BINDING-SITES IN THE DEVELOPING MOUSE PALATE

The distribution of epidermal growth factor (EGF) receptors in the dev eloping mouse palate was mapped using I-125-EGF labeling of paired pal ate organ cultures. I-125-EGF binding sites were localized throughout the palate mesenchyme except in a region immediately adjacent to the m idline seam. The EGF receptor was detected in all palatal epithelia at the beginning of culture, but as seam formation and subsequent degene ration took place it was down-regulated in the medial edge epithelia. Using submerged culture the mechanism of this down-regulation was inve stigated by treating with various growth factors such as EGF, basic fi broblast growth factor (bFGF), insulin-like growth factor-II (IGF-II) and transforming growth factors alpha and beta (TGF-alpha, TGF-beta). Conventional Trowell organ culture was not used because it was observe d that the Millipore filter blocked growth factor uptake. All three TG F-beta isoforms accelerated palate fusion and TGF-beta1 reduced I-125- EGF binding throughout the palate, suggesting a potential level of reg ulation during palatogenesis. Contrary to previous reports, EGF treatm ent in the absence of serum prevented palatal shelf fusion, and also d own-regulated subsequent I-125-EGF binding.