Specification of multiple vertebral identities by ectopically expressed Hoxb-8.

Abstract

We have recently generated Hoxb-8 gain-of-function mutant embryos, using a Hoxb-8 transgene driven by a retinoic acid receptor beta 2 promoter to extend the expression domain to more anterior regions of the embryo (Charité et al. [1994] Cell 78:589-601). Here we describe the phenotype in the axial skeleton of transgenic embryos. The severity of the phenotype was variable, and cervical vertebrae and the base of the skull were affected in different ways. We observed fusion of the anterior arch of the atlas to the dens of the axis, partial splitting of the vertebral body and the neural arch of the axis, and abnormal morphology of the basioccipital and exoccipital bones. The basioccipital bone projected into the atlas, sometimes fusing to the dens of the axis; the exoccipitial bones appeared to be transformed towards neural arch-like structures. A novel pattern of posterior homeotic transformations was observed, involving cervical vertebrae C3 to C7: the ventral aspect of vertebrae C5 to C7 could acquire different morphologies characteristic of more posterior vertebrae: C5 could be transformed into C6, C7, or T1, C6 into C7 or T1, and C7 into T1. Phenotypes of different severity could be arranged into a phenotypic series, starting with the transformation of C7 to T1 and involving transformation of increasingly more anterior vertebrae into increasingly more posterior identities; no vertebra acquired a more posterior morphology than that of the vertebra immediately caudal to it. Ribs appeared to be formed relatively independently of rib heads; cervical ribs (but not rib heads) could be observed as anterior as C3. The results suggest that higher levels of ectopically expressed Hoxb-8 result in specification of more posterior vertebral identities.