Specific craniofacial cartilage dysmorphogenesis coincides with a loss of dlx gene expression in retinoic acid-treated zebrafish embryos

Treatments of zebrafish embryos with retinoic acid (RA), a substance known to cause abnormal craniofacial cartilage development in other vertebrates, result in dose- and stage-dependent losses of dir homeobox gene expression in several regions of the embryo. Dir expression in neural crest cells migrating from the hindbrain and in the visceral arch primordia is particularly sensitive to RA treatment. The strongest effects are observed when RA is administered prior to or during crest cell migration but effects can also be observed if RA is applied when the cells have entered the primordia of the arches. Losses of dir expression correlate either with the loss of cartilage elements originating from hindbrain neural crest cells or with abnormal morphology of these elements. Cartilage elements that originate from midbrain neural crest cells, which do not express dir genes, are less affected. Taken together with the observation that the normal patterns of visceral arch dir expression just prior to cartilage condensation resemble the morphology of the cartilage elements that are about to differentiate, our results suggest that dir genes are an important part of a multi-step process in the development of a subset of craniofacial cartilage elements. (C) 1997 Elsevier Science Ireland Ltd.