Abstract
Hox
genes encode transcription factors that regulate morphogenesis in all animals with bilateral symmetry. Although
Hox
genes have been extensively studied, their molecular function is not clear in vertebrates, and only a limited number of genes regulated by Hox transcription factors have been identified.
Hoxa2
is required for correct development of the second branchial arch, its major domain of expression. We now show that
Meox1
is genetically downstream from
Hoxa2
and is a direct target.
Meox1
expression is downregulated in the second arch of
Hoxa2
mouse mutant embryos. In chromatin immunoprecipitation (ChIP), Hoxa2 binds to the
Meox1
proximal promoter. Two highly conserved binding sites contained in this sequence are required for Hoxa2-dependent activation of the
Meox1
promoter. Remarkably, in the absence of Meox1 and its close homolog Meox2, the second branchial arch develops abnormally and two of the three skeletal elements patterned by Hoxa2 are malformed. Finally, we show that Meox1 can specifically bind the DNA sequences recognized by Hoxa2 on its functional target genes. These results provide new insight into the Hoxa2 regulatory network that controls branchial arch identity.