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Growing Evidence that Periderm is Essential for Orofacial and Epidermal Development
Author(s) -
Schutte Brian C.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.86.2
Subject(s) - biology , zebrafish , genetics , tbx1 , ectoderm , microbiology and biotechnology , gene , embryogenesis , gene expression , promoter
Orofacial clefting is one of the most common birth defects, affecting about 1/700 births world wide. The cause of orofacial clefting is complex, including multiple genetic and environmental factors. To date, genome wide association studies have identified 36 loci that contribute risk, and linkage studies have identified the gene involved in 249 rare syndromes. However, these loci still only account for a fraction of the overall heritability of orofacial clefting. To determine the “missing heritability”, we need a better understanding of the pathological mechanisms that lead to orofacial clefts. Recent human and animal genetic studies suggest that proper periderm development is one essential pathway during palatogenesis. The periderm is the superficial layer of squamous epithelial cells that covers the ectoderm of mammalian embryos. During palatogenesis, the periderm covering the medial edge of the palatal shelves must degenerate at a precise moment to allow palatal fusion. If the periderm degenerates too early, or too late, the palatal shelves may not fuse, leading to a cleft palate. Based on mutant mouse studies, 20 genes have been identified as essential for proper periderm development. Significantly, DNA variation in 13 of the 20 genes causes and/or contributes risk for orofacial clefting in humans, including transcription factors (IRF6, GRHL3, TP63, TBX1, TFAP2A) and cell signaling molecules (FGF10, FGFR2, NOG, RIPK4, TGFB3). Several of these genes were also shown to be required for development of the enveloping layer during zebrafish embryogenesis. Like the mammalian periderm, the enveloping layer is the superficial layer of epithelium that surrounds the zebrafish embryo. The apparently conserved functions of these genes in periderm and enveloping layer has allowed the development of robust functional assays in zebrafish for testing potentially pathogenic mutations found in patient with orofacial cleft. Moreover, the significance of this set of genes is not limited to development, as somatic mutations and altered expression has been associated with cancer, especially squamous cell carcinoma. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .