Gene and protein expression of transforming growth factor beta 2 gene during murine primary palatogenesis.

The molecular mechanisms by which the primordia of the midface grow and fuse to form the primary palate are not well characterized. This is in spite of the fact that failure of growth and/or fusion of these facial primordia leads to the common human craniofacial birth defects, clefts of the lip with or without clefts of the palate. Members of the transforming growth factor beta (Tgfbeta) superfamily have been shown to play critical roles during craniofacial development. Specifically, the role of Tgfbeta-3 in mediating the fusion of the embryonic secondary palatal shelves is well documented. In a screen for genes expressed during fusion of the murine midfacial processes, Tgfbeta2 was identified as a gene differentially expressed during fusion of the lateral and medial nasal processes. The objective of our study was to analyze the spatial and temporal expression of Tgfbeta2 during critical stages of midfacial morphogenesis at both the transcript and protein levels. We also compared the pattern of expression of Tgfbeta2 with that of Bmp4, a gene shown previously to be involved in mediating the fusion process in the midface. Our results showed Tgfbeta2 expression in a very restrictive area of the epithelial layer along the borders of the midfacial primordia, in a pattern very similar to that of Bmp4. The highly restrictive and spatial and temporal pattern of expression of Tgfbeta2 implicates its role in mediating the fusion of the midfacial processes, possibly through interacting with Bmp4 in the regulation of apoptosis and/or epithelial-mesenchymal transformation. A greater understanding of the role of this gene will clarify how the normal midface grows and the mechanisms behind cleft development.