The formation of the palate (palatogenesis) is a complex developmental process that when disrupted results in cleft palate, a common human birth defect, occurring in 1 out of every 2000 babies. The palate is formed from a pair of palatal shelves composed of a mesenchymal core covered by a layer of surface epithelium. Additionally, prefusion palatal shelves are covered by a thin layer of transient peridermal cells. The shelves grow downwards along each side of the tongue, elevate and fuse forming the midline epithelial seam (MES), which is subsequently removed to form a fused palate. The TGF-β superfamily plays an essential role in MES removal as well as in craniofacial growth and patterning. Here we examine the mechanism of Smad-dependent (canonical) and Smad-independent (non-canonical) signaling in the palatal mesenchyme and epithelium, and the regulation of Tgfb3 palatal expression
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