HOX GROUP-3 PARALOGS REGULATE THE DEVELOPMENT AND MIGRATION OF THE THYMUS, THYROID, AND PARATHYROID-GLANDS

The thymus, thyroid, and parathyroid glands in vertebrates develop fro m the pharyngeal region, with contributions both from pharyngeal endod erm and from neural crest cells in the pharyngeal arches. Hoxa3 mutant homozygotes have defects in the development of all three organs. Role s for the Hoxa3 paralogs, Hoxb3 and Hoxd3, were investigated by examin ing various mutant combinations. The thyroid defects seen in Hoxa3 sin gle mutants are exacerbated in double mutants with either of its paral ogs, although none of the double-mutant combinations resulted in thyro id agenesis. The results indicate that the primary role of these genes in thyroid development is their effect on the development and migrati on of the ultimobranchial bodies, which contribute the parafollicular or C-cells to the thyroid. Hoxb3,Hoxd3 double mutants show no obvious defects in the thymus or parathyroids. However, the removal of one fun ctional copy of Hoxa3 from the Hoxb3,Hoxd3 double mutants (Hoxa3(+/-), Hoxb3(-/-),Hoxd3(-/-)) results in the failure of the thymus and parath yroid glands to migrate to their normal positions in the throat. Very little is known about the molecular mechanisms used to mediate the mov ement of tissues during development. These results indicate that Hoxa3 , Hoxb3, and Hoxd3 have highly overlapping functions in mediating the migration of pharyngeal organ primordia. In addition, Hoxa3 has a uniq ue function with respect to its paralogs in thymus, parathyroid, and t hyroid development, This unique function may be conferred by the expre ssion of Hoxa3, but not Hoxb3 nor Hoxd3, in the pharyngeal pouch endod erm. (C) 1998 Academic Press.