SATB2 Is a Multifunctional Determinant of Craniofacial Patterning and Osteoblast Differentiation
Copyright policy )SATB2 Is a Multifunctional Determinant of Craniofacial Patterning and Osteoblast Differentiation
Vertebrate skeletogenesis involves two processes, skeletal patterning and osteoblast differentiation. Here, we show that Satb2, encoding a nuclear matrix protein, is expressed in branchial arches and in cells of the osteoblast lineage. Satb2-/- mice exhibit both craniofacial abnormalities that resemble those observed in humans carrying a translocation in SATB2 and defects in osteoblast differentiation and function. Multiple osteoblast-specific genes were identified as targets positively regulated by SATB2. In addition, SATB2 was found to repress the expression of several Hox genes including Hoxa2, an inhibitor of bone formation and regulator of branchial arch patterning. Molecular analysis revealed that SATB2 directly interacts with and enhances the activity of both Runx2 and ATF4, transcription factors that regulate osteoblast differentiation. This synergy was genetically confirmed by bone formation defects in Satb2/Runx2 and Satb2/Atf4 double heterozygous mice. Thus, SATB2 acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation.
- Baylor College of Medicine United States
- Max Planck Society Germany
Homeodomain Proteins, Mice, Knockout, Osteoblasts, Biochemistry, Genetics and Molecular Biology(all), Skull, Genes, Homeobox, Gene Expression Regulation, Developmental, Cell Differentiation, Core Binding Factor Alpha 1 Subunit, Matrix Attachment Region Binding Proteins, Activating Transcription Factor 4, Facial Bones, Craniofacial Abnormalities, Repressor Proteins, Mice, Branchial Region, Osteogenesis, Mutation, Animals, Body Patterning, Transcription Factors
Homeodomain Proteins, Mice, Knockout, Osteoblasts, Biochemistry, Genetics and Molecular Biology(all), Skull, Genes, Homeobox, Gene Expression Regulation, Developmental, Cell Differentiation, Core Binding Factor Alpha 1 Subunit, Matrix Attachment Region Binding Proteins, Activating Transcription Factor 4, Facial Bones, Craniofacial Abnormalities, Repressor Proteins, Mice, Branchial Region, Osteogenesis, Mutation, Animals, Body Patterning, Transcription Factors
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).475 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 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!