Expression and requirement of T-box transcription factors Tbx2 and Tbx3 during secondary palate development in the mouse.
Formation of the mammalian secondary palate is a highly regulated and complex process. Impairment of the underlying cellular and molecular programs often results in cleft palate, a common birth defect in mammals. Here we report that Tbx2 and Tbx3, two closely related genes encoding T-box transcription factors, are expressed in the mesenchyme of the mouse palatal structures during development. Mice homozygous mutant for Tbx2 and mice double heterozygous for Tbx2 and Tbx3 exhibit a cleft palate phenotype arguing for an important contribution of Tbx2 and Tbx3 to palatogenesis. In Tbx2-deficient embryos, the bilateral primordial palatal shelves form but are smaller and retarded in the outgrowth process. They do not make contact but retain the potential to fuse. Development of other craniofacial structures appears normal, suggesting that impaired palate formation in Tbx2-mutant mice is caused by a primary defect in the palatal shelf mesenchyme. This is further supported by increased cell proliferation and apoptosis accompanied by increased expression of Bmp4 and CyclinD1 in Tbx2-deficient palatal shelves. Hence, Tbx2 and Tbx3 function overlappingly to control growth of the palatal shelf mesenchyme.
Zirzow
Susann
S
Institut für Molekularbiologie, OE5250, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany.
Lüdtke
Timo H-W
TH
Brons
Janynke F
JF
Petry
Marianne
M
Christoffels
Vincent M
VM
Kispert
Andreas
A
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D010159:Palate / Q000196:embryology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000502:physiology
D055415:Bone Morphogenetic Protein 4; C530105:Ccnd1 protein, mouse; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse; D019938:Cyclin D1