Homeodomain transcription factors control developmental processes. They pattern body formation, specify cell lineages and switch the onset of gene regulatory cascades. Pitx2, a bicoid-related homeodomain transcription factor, is asymmetrically expressed in the left lateral plate mesoderm and mesoderm-derived tissues. Pitx2 null mice are characterized by failure of body wall closure, axial and cardiac malformations and arrest of organ development. By analyzing Pitx2 expression pattern and phenotype of Pitx2 null mice, we have established that (1) Pitx2 is a universal muscle marker, because it marks the muscle lineage more completely that any of the known markers, (2) expression of Pitx2 precedes the onset of myogenic progression in the cephalic mesoderm and mesodermal core of first BA and activates the transcription factors Tbx1, Tcf21, and Msc, (3) Pitx2 follows the onset of myogenic progression in the somitic mesoderm, (4) loss of Pitx2 leads to absence of extraocular, mastication and abdominal muscles and distortion in trunk muscles. In addition, DNA microarray analysis of limb pre-myogenic progenitor cells indicates that Pitx2 regulates several transcription factors and structural proteins. These observations support the idea that Pitx2 has a function in the maturation of skeletal muscles.
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