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Publication : TGFβ3 regulates periderm removal through ΔNp63 in the developing palate.

First Author  Hu L Year  2015
Journal  J Cell Physiol Volume  230
Issue  6 Pages  1212-25
PubMed ID  25358290 Mgi Jnum  J:315539
Mgi Id  MGI:6829185 Doi  10.1002/jcp.24856
Citation  Hu L, et al. (2015) TGFbeta3 regulates periderm removal through DeltaNp63 in the developing palate. J Cell Physiol 230(6):1212-25
abstractText  The periderm is a flat layer of epithelium created during embryonic development. During palatogenesis, the periderm forms a protective layer against premature adhesion of the oral epithelia, including the palate. However, the periderm must be removed in order for the medial edge epithelia (MEE) to properly adhere and form a palatal seam. Improper periderm removal results in a cleft palate. Although the timing of transforming growth factor beta3 (TGFbeta3) expression in the MEE coincides with periderm degeneration, its role in periderm desquamation is not known. Interestingly, murine models of knockout (-/-) TGFbeta3, interferon regulatory factor 6 (IRF6) (-/-), and truncated p63 (DeltaNp63) (-/-) are born with palatal clefts because of failure of the palatal shelves to adhere, suggesting that these genes regulate palatal epithelial differentiation. However, despite having similar phenotypes in null mouse models, no studies have analyzed the possible association between the TGFbeta3 signaling cascade and the IRF6/DeltaNp63 genes during palate development. Recent studies indicate that regulation of DeltaNp63, which depends on IRF6, facilitates epithelial differentiation. We performed biochemical analysis, gene activity and protein expression assays with palatal sections of TGFbeta3 (-/-), DeltaNp63 (-/-), and wild-type (WT) embryos, and primary MEE cells from WT palates to analyze the association between TGFbeta3 and IRF6/DeltaNp63. Our results suggest that periderm degeneration depends on functional TGFbeta3 signaling to repress DeltaNp63, thereby coordinating periderm desquamation. Cleft palate occurs in TGFbeta3 (-/-) because of inadequate periderm removal that impedes palatal seam formation, while cleft palate occurs in DeltaNp63 (-/-) palates because of premature fusion.
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