Multiple functions of Snail family genes during palate development in mice.
Palate development requires precise regulation of gene expression changes, morphogenetic movements and alterations in cell physiology. Defects in any of these processes can result in cleft palate, a common human birth defect. The Snail gene family encodes transcriptional repressors that play essential roles in the growth and patterning of vertebrate embryos. Here we report the functions of Snail (Snai1) and Slug (Snai2) genes during palate development in mice. Snai2(-/-) mice exhibit cleft palate, which is completely penetrant on a Snai1 heterozygous genetic background. Cleft palate in Snai1(+/-) Snai2(-/-) embryos is due to a failure of the elevated palatal shelves to fuse. Furthermore, while tissue-specific deletion of the Snai1 gene in neural crest cells does not cause any obvious defects, neural-crest-specific Snai1 deletion on a Snai2(-/-) genetic background results in multiple craniofacial defects, including a cleft palate phenotype distinct from that observed in Snai1(+/-) Snai2(-/-) embryos. In embryos with neural-crest-specific Snai1 deletion on a Snai2(-/-) background, palatal clefting results from a failure of Meckel's cartilage to extend the mandible and thereby allow the palatal shelves to elevate, defects similar to those seen in the Pierre Robin Sequence in humans.
Murray
Stephen A
SA
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Oram
Kathleen F
KF
Gridley
Thomas
T
D000818:Animals; D000831:Animals, Newborn; D002972:Cleft Palate / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008334:Mandible / Q000196:embryology; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology / Q000196:embryology; D010159:Palate / Q000196:embryology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C000604429:Snai1 protein, mouse; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors