Cell proliferation and expression of EGF, TGF-alpha, and EGF receptor in the developing primary palate

Growth factors such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) play an important role in cell proliferation during embryogenesis. The purposes of the study were to characterize the expression patterns of EGF and TGF-alpha and their receptor, EGF receptor (EGF-R), and to analyze regional patterns of cell proliferation during primary palate morphogenesis when facial primordia outgrow and fuse to form the premaxillary and upper lip regions. The expression of all molecules was studied with indirect immunohistochemistry with conventional and/or confocal microscopes in normal days 10 and 11 CD1 mice. 5-Bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) were used as markers of cell proliferation. EGF, TGF-alpha, and EGF-R were found to have similar distribution patterns at all stages examined. In the anterior region of the face, the molecules were intensely localized at the tips and peripheral regions of the medial and lateral nasal prominences. Upon fusion of the facial prominences, all three molecules were present mainly at the fusion area and the tips and peripheral areas of the maxillary and nasal prominences. BrdU and PCNA were found to have distribution patterns similar to those of EGF, TGF-alpha, and EGF-R, with intense staining at the tips and peripheral regions of the facial prominences. These results show that EGF, TGF-alpha, and their receptor were expressed more intensely in regions of the developing primary palate where cell proliferation was most pronounced, and suggest that EGF, TGF-alpha, and EGF-R may play a role in cell proliferation during morphogenesis of the primary palate.