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Publication : Pitx2 is an upstream activator of extraocular myogenesis and survival.

First Author  Zacharias AL Year  2011
Journal  Dev Biol Volume  349
Issue  2 Pages  395-405
PubMed ID  21035439 Mgi Jnum  J:168032
Mgi Id  MGI:4881620 Doi  10.1016/j.ydbio.2010.10.028
Citation  Zacharias AL, et al. (2011) Pitx2 is an upstream activator of extraocular myogenesis and survival. Dev Biol 349(2):395-405
abstractText  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.
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