PUBLICATION
Pbx homeodomain proteins direct Myod activity to promote fast-muscle differentiation
- Authors
- Maves, L., Waskiewicz, A.J., Paul, B., Cao, Y., Tyler, A., Moens, C.B., and Tapscott, S.J.
- ID
- ZDB-PUB-070820-13
- Date
- 2007
- Source
- Development (Cambridge, England) 134(18): 3371-3382 (Journal)
- Registered Authors
- Maves, Lisa, Moens, Cecilia, Waskiewicz, Andrew
- Keywords
- none
- Datasets
- GEO:GSE8428
- MeSH Terms
-
- Animals
- Gene Expression
- Gene Expression Regulation, Developmental*
- Hedgehog Proteins/genetics
- Hedgehog Proteins/metabolism
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism*
- Muscle Development/genetics*
- Muscle, Skeletal/embryology*
- Muscle, Skeletal/metabolism
- MyoD Protein/genetics
- MyoD Protein/metabolism*
- Myogenin/metabolism
- Oligonucleotide Array Sequence Analysis
- RNA, Messenger/analysis
- RNA, Messenger/metabolism
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 17699609 Full text @ Development
Citation
Maves, L., Waskiewicz, A.J., Paul, B., Cao, Y., Tyler, A., Moens, C.B., and Tapscott, S.J. (2007) Pbx homeodomain proteins direct Myod activity to promote fast-muscle differentiation. Development (Cambridge, England). 134(18):3371-3382.
Abstract
The basic helix-loop-helix (bHLH) transcription factor Myod directly regulates gene expression throughout the program of skeletal muscle differentiation. It is not known how a Myod-driven myogenic program is modulated to achieve muscle fiber-type-specific gene expression. Pbx homeodomain proteins mark promoters of a subset of Myod target genes, including myogenin (Myog); thus, Pbx proteins might modulate the program of myogenesis driven by Myod. By inhibiting Pbx function in zebrafish embryos, we show that Pbx proteins are required in order for Myod to induce the expression of a subset of muscle genes in the somites. In the absence of Pbx function, expression of myog and of fast-muscle genes is inhibited, whereas slow-muscle gene expression appears normal. By knocking down Pbx or Myod function in combination with another bHLH myogenic factor, Myf5, we show that Pbx is required for Myod to regulate fast-muscle, but not slow-muscle, development. Furthermore, we show that Sonic hedgehog requires Myod in order to induce both fast- and slow-muscle markers but requires Pbx only to induce fast-muscle markers. Our results reveal that Pbx proteins modulate Myod activity to drive fast-muscle gene expression, thus showing that homeodomain proteins can direct bHLH proteins to establish a specific cell-type identity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping