Hoxa-3

Abstract

Hoxa-3 is expressed in embryos beginning at E7.5 in posterior ectoderm and mesoderm, and at later stages in the caudal hindbrain, associated migrating neural crest cells, pharyngeal arches, pharyngeal pouch endoderm, cranial ganglia, and somitic mesoderm. It is also expressed in the developing forelimb bud. This chapter presents a study in which Hoxa-3 mutants had a spectrum of abnormalities in the tissues and structures primarily derived from the neural crest and pharyngeal endoderm of the third and fourth pharyngeal arches and pouches. The defects include deletions and malformations of the throat cartilages, deletions of the thymus and parathyroids, and thyroid hypoplasia. Hoxa-3 mutants also had defects in the development of the IXth and Xth cranial nerves, with fusions of these two nerves or failure of the IXth cranial ganglion to connect to the hindbrain. Neural crest cell number, migration, and marker gene expression appeared normal. These results suggest that Hoxa-3 affects the patterning or differentiation of the neural crest, or its ability to interact with other cell types such as the pharyngeal endoderm, where Hoxa-3 is also expressed. The phenotype of the Hoxa-3 mutant was strikingly similar to DiGeorge syndrome in humans suggesting Hoxa-3 may be part of the same developmental pathway that is defective in the DiGeorge patients.