RARbeta mediates the response of Hoxd4 and Hoxb4 to exogenous retinoic acid.

One action of retinoids in development is the regulation of Hox gene expression. Hoxd4 and Hoxb4 expression in the embryonic hindbrain is anteriorized by retinoic acid (RA) treatment of mid-gestation mouse embryos. Here we demonstrate that retinoic acid receptor beta (Rarb) deficient mice present only a partial anteriorization of either Hoxd4 or Hoxb4 in response to RA treatment. Our results strongly suggest that RARbeta is a mediator of their RA-response, and reveal anteroposterior polarity within a single rhombomere (r). Additionally, we generated mice doubly mutated for Hoxd4 and Rarb in an attempt to identify common morphogenetic pathways between these two genes. We conclude that there are no synergistic interactions between Hoxd4 and Rarb in the specification of the cervical vertebrae.