Pitx2 promotes development of splanchnic mesoderm-derived branchiomeric muscle

Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, TX 77030, USA.
Development (Impact Factor: 6.46). 01/2007; 133(24):4891-9. DOI: 10.1242/dev.02693
Source: PubMed


Recent experiments, showing that both cranial paraxial and splanchnic mesoderm contribute to branchiomeric muscle and cardiac outflow tract (OFT) myocardium, revealed unexpected complexity in development of these muscle groups. The Pitx2 homeobox gene functions in both cranial paraxial mesoderm, to regulate eye muscle, and in splanchnic mesoderm to regulate OFT development. Here, we investigated Pitx2 in branchiomeric muscle. Pitx2 was expressed in branchial arch core mesoderm and both Pitx2 null and Pitx2 hypomorphic embryos had defective branchiomeric muscle. Lineage tracing with a Pitx2cre allele indicated that Pitx2 mutant descendents moved into the first branchial arch. However, markers of both undifferentiated core mesoderm and specified branchiomeric muscle were absent. Moreover, lineage tracing with a Myf5cre allele indicated that branchiomeric muscle specification and differentiation were defective in Pitx2 mutants. Conditional inactivation in mice and manipulation of Pitx2 expression in chick mandible cultures revealed an autonomous function in expansion and survival of branchial arch mesoderm.

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    • "Considerable overlap in the expression of head muscle markers [e.g., Myf5, Tcf21 (capsulin), Msc (MyoR), Tbx1, Pitx2] and cardiac markers such as Islet1 and Nkx2.5 is evident in the pharyngeal mesoderm, suggesting that these cells play a dual role in myogenesis and cardiogenesis (Bothe and Dietrich 2006; Nathan et al. 2008; Tirosh-Finkel et al. 2006). Likewise, lineage studies in the mouse demonstrated an overlap in progenitor populations contributing to pharyngeal muscles and second heart field derivatives (Dong et al. 2006; Harel et al. 2009; Nathan et al. 2008; Verzi et al. 2005) (Fig. 2). A genetic link between Tcf21, Tbx1, and Lhx2 within the pharyngeal mesoderm was recently documented (Harel et al. 2012). "
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    • "Another fascinating difference is that Mrf4, which is important for myogenic determination of limb and trunk progenitors, cannot fulfil the same role in the head [26]. It is now known that all the head muscles depend on Pitx2 and Tbx1, which are transcription factors that contain homeodomains, and which positively regulate one another as well as Myf5; Pitx2 and Tbx1 thus regulate the myogenic cascade [61–63]. Recently, it has been shown that only the extraocular eye muscle, and not other head muscles, depends on the presence of both Myf5 and Mrf4, whereby MyoD cannot compensate for their absence [64]. "
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    Cellular and Molecular Life Sciences CMLS 03/2014; 71(16). DOI:10.1007/s00018-014-1604-5 · 5.81 Impact Factor
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    • "Although Pitx expression has been detected in muscle precursors during development (Dong et al., 2006; L'Honore et al., 2007; Shih et al., 2007a), little is known of the expression dynamics (Ono et al., 2010) or function of Pitx genes during myogenic progression in muscle satellite cells. We used the isolated myofibre model to explore Pitx expression in quiescent and activated satellite cells, and in satellite cell-derived myoblasts during proliferation and commitment to differentiation. "
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    ABSTRACT: Skeletal muscle retains a resident stem cell population called satellite cells. Although mitotically quiescent in mature muscle, satellite cells can be activated to produce myoblast progeny to generate myonuclei for skeletal muscle homoeostasis, hypertrophy and repair. Regulation of satellite cell function in adult requires redeployment of many of the regulatory networks fundamental to developmental myogenesis. Involved in such control of muscle stem cell fate in embryos are members of the Pitx gene family of bicoid-class homeodomain proteins. Here, we investigated the expression and function of all three Pitx genes in muscle satellite cells of adult mice. Endogenous Pitx1 was undetectable, whilst Pitx2a, Pitx2b and Pitx2c were at low levels in proliferating satellite cells, but increased during the early stages of myogenic differentiation. By contrast, proliferating satellite cells expressed robust amounts of Pitx3, with levels then decreasing as cells differentiated, although Pitx3 remained expressed in unfused myoblasts. To examine the role of Pitx genes in satellite cell function, retroviral-mediated expression of Pitx1, all Pitx2 isoforms or Pitx3, was used. Constitutive expression of any Pitx isoform suppressed satellite cell proliferation, with the cells undergoing enhanced myogenic differentiation. Conversely, myogenic differentiation into multinucleated myotubes was decreased when Pitx2 or Pitx3 levels were reduced using siRNA. Together, our results show that Pitx genes play a role in regulating satellite cell function during myogenesis in adult.
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