A Crucial Role forPax3in the Development of the Hypaxial Musculature and the Long-Range Migration of Muscle Precursors

Abstract

Activated by dorsalizing and lateralizing signals, the Pax3 gene is an early marker for the entire paraxial mesoderm and its dorsal derivative, the dermomyotome. Later, its expression becomes restricted to the lateral dermomyotome and to the migratory muscle precursors giving rise to the hypaxial musculature. To understand better the role that Pax3 plays during development of paraxial mesoderm-derived structures, we followed the development of the musculature and skeleton in the murine Pax3 mutant Splotch. We found that the mutant dermomyotomes and myotomes failed to organize and to elongate medially and laterally, leading to the reduction and malformation of the entire trunk musculature. Mutants lacked ventral aspects of the body wall musculature and muscles derived from migratory myoblasts, suggesting a crucial function for Pax3 in the long-range migration of muscle precursors giving rise to the ventral hypaxial musculature. In addition, severe malformations were detected in the skeleton. The axial and appendicular skeleton displayed malformations and in particular multiple bone fusions.

Cell-type-specific regulation of distinct sets of gene targets by Pax3 and Pax3/FKHR

“…PD sites are also found in the analogous region of the putative murine Cnr1 gene, although not strictly conserved positionally. Expression of CNR1 during embryogenesis in the developing brain and neural tube (Buckley et al, 1998) in a pattern overlapping that of Pax3 (Goulding et al, 1991;Dietrich et al, 1993;Gerard et al, 1995;Terzic and SaragaBabic, 1999) as well as the role of CNR1 (Song and Zhong, 2000) and Pax3 (Epstein et al, 1996;Conway et al, 1997a;Tremblay et al, 1998) in cell migration are consistent with Pax3 potentially regulating CNR1 expression directly.…”

Pax3 activation promotes the differentiation of mesenchymal stem cells toward the myogenic lineage

“…This later defect is associated with a lack of migratory muscle progenitors, which prevents MyoD activation by Myf5 and Mrf4 [20,28,36,37]. Because of this important role in muscle specification, Pax3 is considered a master regulator of the embryonic myogenic program [24,27].…”

“…At this site myogenesis occurs [25,26] upon activation of MRFs, including Myf-5, Mrf4, MyoD, and myogenin. Since the role of Pax3 upstream of MRFs is essential for embryonic muscle specification [18,19,24,[27][28][29][30], we investigated the potential of Pax3 to drive myogenesis from a murine MSC as well as its effects on other mesenchymal lineages.…”

Extracellular matrix remodeling accompanies axial muscle development and morphogenesis in the mouse

“…Remarkably, in amniote embryos, the myotome is only a transient structure and does not get innervated (Deries et al, 2008). Rather, the segmented myotomes are transformed: epaxially into the complex deep back muscles and hypaxially into the intercostal and body wall muscles (Christ et al, 1983;Tremblay et al, 1998;Kalcheim et al, 1999;Deries et al, 2010).…”