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PMID:21035439

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Citation

Zacharias, AL, Lewandoski, M, Rudnicki, MA and Gage, PJ (2011) Pitx2 is an upstream activator of extraocular myogenesis and survival. Dev. Biol. 349:395-405

Abstract

The transcription factors required to initiate myogenesis in branchial arch- and somite-derived muscles are known, but the comparable upstream factors required during extraocular muscle development have not been identified. We show Pax7 is dispensable for extraocular muscle formation, whereas Pitx2 is cell-autonomously required to prevent apoptosis of the extraocular muscle primordia. The survival requirement for Pitx2 is stage-dependent and ends following stable activation of genes for the muscle regulatory factors (e.g. Myf5, MyoD), which is reduced in the absence of Pitx2. Further, PITX2 binds and activates transcription of the Myf5 and MyoD promoters, indicating these genes are direct targets. Collectively, these data demonstrate that PITX2 is required at several steps in the development of extraocular muscles, acting first as an anti-apoptotic factor in pre-myogenic mesoderm, and subsequently to activate the myogenic program in these cells. Thus, Pitx2 is the first demonstrated upstream activator of myogenesis in the extraocular muscles.

Links

PubMed PMC3019256 Online version:10.1016/j.ydbio.2010.10.028

Keywords

Animals; Apoptosis/genetics; Apoptosis/physiology; Cell Survival; Chromatin Immunoprecipitation; Homeodomain Proteins/metabolism; In Situ Hybridization; Mesoderm/metabolism; Mesoderm/physiology; Mice; Muscle Development/physiology; Myogenic Regulatory Factors/metabolism; Oculomotor Muscles/embryology; PAX7 Transcription Factor/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PITX2

acts_upstream_of_or_within

GO:0002074: extraocular skeletal muscle development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1857844
MGI:MGI:1857846

P

  • results_in_development_of:(EMAPA:16039)

Seeded From UniProt

complete

MOUSE:PITX2

enables

GO:0031490: chromatin DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97252)|has_input:(MGI:MGI:97275)

Seeded From UniProt

complete

MOUSE:PITX2

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:PITX2

acts_upstream_of_or_within

GO:0043388: positive regulation of DNA binding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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