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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    • "ts an ancient patterning mechanism ( Chapman et al . 1996 ; Gage et al . 1999 ; Kitamura et al . 1999 ; Lu et al . 2002 ) . A loss of Pitx2 function in mouse reflects its early expression in anterior cranial mesoderm : eye and mandibular arch muscles are lost or severely hypoplastic , but hyoid and branchial arch mus - cles are mostly unaffected ( Dong et al . 2006 ) . Mice lacking Tbx1 function show a number of craniofacial abnormalities such as losses of posterior pharyngeal arch - derived muscles ( Lindsay et al . 2001 ) . A conditional loss of Tbx1 function in the mesoderm using the Mesp1 : Cre line causes a loss of the branchial and hyoid arch - derived muscles but does not severely affect th"
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