Cooperation of Hoxa5 and Pax1 genes during formation of the pectoral girdle

Abstract

Hox and Pax transcription factors are master regulators of skeletal and organ morphogenesis. Some skeletal malformations encountered in Hoxa5 mutants are shared by the undulated (un) mice, which bear a point mutation in the Pax1 gene. To investigate whether Hoxa5 and Pax1 act in common pathways during skeletal development, we analyzed Hoxa5;un compound mutants. Our genetic studies show that Hoxa5 and Pax1 cooperate in the vertebral patterning of the cervicothoracic transition region and in acromion morphogenesis. The dynamics of expression of Hoxa5 and Pax1 in the pectoral girdle region suggest that both genes function in a complementary fashion during acromion formation. Whereas Pax1 is required for the recruitment of acromion precursor cells, Hoxa5 may provide regional cues essential for the correct formation of the acromion by ensuring Pax1 expression at the proper time and position during morphogenesis of the pectoral girdle. Hoxa5 also has a distinctive role in specifying the fate of perichondrial and chondrogenic cell lineages in a Sox9-dependent way.