Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development
Bmp signaling regulates a dose-dependent transcriptional program to control facial skeletal development
We performed an in depth analysis of Bmp4, a critical regulator of development, disease, and evolution, in cranial neural crest (CNC). Conditional Bmp4 overexpression, using a tetracycline-regulated Bmp4 gain-of-function allele, resulted in facial skeletal changes that were most dramatic after an E10.5 Bmp4 induction. Expression profiling uncovered a signature of Bmp4-induced genes (BIG) composed predominantly of transcriptional regulators that control self-renewal, osteoblast differentiation and negative Bmp autoregulation. The complimentary experiment, CNC inactivation of Bmp2, Bmp4 and Bmp7, resulted in complete or partial loss of multiple CNC-derived skeletal elements, revealing a crucial requirement for Bmp signaling in membranous bone and cartilage development. Importantly, the BIG signature was reduced in Bmp loss-of-function mutants, indicating Bmp-regulated target genes are modulated by Bmp dose. Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation. These data support the hypothesis that Bmp signaling regulates craniofacial skeletal development by balancing self-renewal and differentiation pathways in CNC progenitors.
- Baylor College of Medicine United States
- The University of Texas System United States
- The Texas Heart Institute United States
- Texas A&M Health Science Center United States
Base Sequence, Bone Morphogenetic Protein 7, Gene Expression Profiling, Molecular Sequence Data, Skull, Bone Morphogenetic Protein 2, Gene Expression Regulation, Developmental, Cell Differentiation, Mice, Transgenic, Bone Morphogenetic Protein 4, Mandible, Embryo, Mammalian, Facial Bones, Mice, Neural Crest, Morphogenesis, Animals, Humans, Sequence Alignment, Signal Transduction
Base Sequence, Bone Morphogenetic Protein 7, Gene Expression Profiling, Molecular Sequence Data, Skull, Bone Morphogenetic Protein 2, Gene Expression Regulation, Developmental, Cell Differentiation, Mice, Transgenic, Bone Morphogenetic Protein 4, Mandible, Embryo, Mammalian, Facial Bones, Mice, Neural Crest, Morphogenesis, Animals, Humans, Sequence Alignment, Signal Transduction
66 Research products, page 1 of 7
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
chevron_left - 1
- 2
- 3
- 4
- 5
chevron_right
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).159 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
