TGF-β type I receptor Alk5 regulates tooth initiation and mandible patterning in a type II receptor-independent manner
Copyright policy )TGF-β type I receptor Alk5 regulates tooth initiation and mandible patterning in a type II receptor-independent manner
TGF-beta superfamily members signal through a heteromeric receptor complex to regulate craniofacial development. TGF-beta type II receptor appears to bind only TGF-beta, whereas TGF-beta type I receptor (ALK5) also binds to ligands in addition to TGF-beta. Our previous work has shown that conditional inactivation of Tgfbr2 in the neural crest cells of mice leads to severe craniofacial bone defects. In this study, we examine and compare the defects of TGF-beta type II receptor (Wnt1-Cre;Tgfbr2(fl/fl)) and TGF-beta type I receptor/Alk5 (Wnt1-Cre;Alk5(fl)(/fl)) conditional knockout mice. Loss of Alk5 in the neural crest tissue resulted in phenotypes not seen in the Tgfbr2 mutant, including delayed tooth initiation and development, defects in early mandible patterning and altered expression of key patterning genes including Msx1, Bmp4, Bmp2, Pax9, Alx4, Lhx6/7 and Gsc. Alk5 controls the survival of CNC cells by regulating expression of Gsc and other genes in the proximal aboral region of the developing mandible. We conclude that ALK5 regulates tooth initiation and early mandible patterning through a pathway independent of Tgfbr2. There is an intrinsic requirement for Alk5 signal in regulating the fate of CNC cells during tooth and mandible development.
- University of California System United States
- University of Southern California United States
- Children's Hospital of Los Angeles United States
TGF-β, Mouse, Lymphoid Enhancer-Binding Factor 1, Receptor, Transforming Growth Factor-beta Type I, Apoptosis, Mandible, Protein Serine-Threonine Kinases, Models, Biological, Alk5, Mice, Animals, Hedgehog Proteins, Dental Enamel, Molecular Biology, Body Patterning, Mice, Knockout, Integrases, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Biology, Embryo, Mammalian, Phenotype, Neural Crest, Mutation, Tooth, Craniofacial development, Gene Deletion, Developmental Biology
TGF-β, Mouse, Lymphoid Enhancer-Binding Factor 1, Receptor, Transforming Growth Factor-beta Type I, Apoptosis, Mandible, Protein Serine-Threonine Kinases, Models, Biological, Alk5, Mice, Animals, Hedgehog Proteins, Dental Enamel, Molecular Biology, Body Patterning, Mice, Knockout, Integrases, Gene Expression Regulation, Developmental, Cell Differentiation, Cell Biology, Embryo, Mammalian, Phenotype, Neural Crest, Mutation, Tooth, Craniofacial development, Gene Deletion, Developmental Biology
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