Palate Development Revealed

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Science  28 Oct 2011:
Vol. 334, Issue 6055, pp. 434
DOI: 10.1126/science.334.6055.434-b

Disruptions of cellular migration, proliferation, differentiation, and apoptosis during development can lead to serious defects. Cleft lip and/or palate, a defect seen in 1 in 700 live births, occur when the plates in the roof of the mouth do not join correctly during embryonic development. Previous work has shown that the mutation of several genes, including WNT, FGF, P63, and IRF6, result in clefting in humans and mice, but how these pathways interact to regulate this process is not well understood. Ferretti et al. now show that cephalic ectoderm-specific deletion of Pbx, which encodes a transcription factor, in mice results in cleft lip and palate. Pbx binds to a specific regulatory element of Wnt9b-Wnt3, which is known to regulate p63. The genetic module Pbx-Wnt-p63, along with downstream Irf6, specifies correct embryonic apoptosis, and misregulation of these elements led to craniofacial defects. Clefting could be repaired by ectopically expressing Wnt in the ectoderm of Pbx mutant mice. Because there are many conserved developmental pathways among mammals, this mouse model will probably be useful to elucidating the mechanisms underlying cleft lip and/or palate in humans.

Dev. Cell. 21, 627 (2011).

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