Analysis of Hox gene expression during early avian heart development

The anteroposterior (A-P) patterning of the developing heart underlies atrial and ventricular lineage specification and heart chamber morphogenesis. The posteriorization of cardiomyogenic phenotype with retinoic acid (RA) treatment of primitive streak stage chicken embryos is suggestive of a role for the clustered homeobox (Hox) genes in early heart patterning (Yutzey et al. [1994] Development 120:871-873; [1995] Dev. Biol. 170:531-541). A screen for Hox genes expressed in chick heart primordia and primitive heart led to the isolation of anterior genes of the Hox clusters expressed during cardiogenesis. Specific hoxd-3, hoxa-4, and hoxd-4 transcripts were detected at the early stages of heart formation and full-length cDNA clones were isolated. Expression of hoxd-3 was detected in the heart forming region of embryos prior to heart tube formation. Expression of hoxa-4, hoxd-3, and hoxb-5 was increased in cardiogenic tissue treated with RA in culture conditions that also produced changes in positionally restricted cardiomyogenic phenotypes. Hox genes expressed in cardiac explants exhibited distinct sensitivities to RA and ouabain treatment when compared to genes, such as nkx-2.5, that are involved in cardiac commitment and differentiation. These studies support a role for Hox genes in early heart patterning and suggest that positional information in the cardiogenic region is established by regulatory mechanisms distinct from early heart lineage specification.