HoxGroup 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands

NR Manley, MR Capecchi - Developmental biology, 1998 - Elsevier
NR Manley, MR Capecchi
Developmental biology, 1998Elsevier
The thymus, thyroid, and parathyroid glands in vertebrates develop from the pharyngeal
region, with contributions both from pharyngeal endoderm and from neural crest cells in the
pharyngeal arches. Hoxa3mutant homozygotes have defects in the development of all three
organs. Roles for theHoxa3paralogs, Hoxb3andHoxd3, were investigated by examining
various mutant combinations. The thyroid defects seen inHoxa3single mutants are
exacerbated in double mutants with either of its paralogs, although none of the double …
The thymus, thyroid, and parathyroid glands in vertebrates develop from the pharyngeal region, with contributions both from pharyngeal endoderm and from neural crest cells in the pharyngeal arches.Hoxa3mutant homozygotes have defects in the development of all three organs. Roles for theHoxa3paralogs,Hoxb3andHoxd3,were investigated by examining various mutant combinations. The thyroid defects seen inHoxa3single mutants are exacerbated in double mutants with either of its paralogs, although none of the double-mutant combinations resulted in thyroid agenesis. The results indicate that the primary role of these genes in thyroid development is their effect on the development and migration of the ultimobranchial bodies, which contribute the parafollicular or C-cells to the thyroid.Hoxb3,Hoxd3double mutants show no obvious defects in the thymus or parathyroids. However, the removal of one functional copy ofHoxa3from theHoxb3,Hoxd3double mutants (Hoxa3+/−,Hoxb3−/−,Hoxd3−/−) results in the failure of the thymus and parathyroid glands to migrate to their normal positions in the throat. Very little is known about the molecular mechanisms used to mediate the movement of tissues during development. These results indicate thatHoxa3, Hoxb3,andHoxd3have highly overlapping functions in mediating the migration of pharyngeal organ primordia. In addition,Hoxa3has a unique function with respect to its paralogs in thymus, parathyroid, and thyroid development. This unique function may be conferred by the expression ofHoxa3,but notHoxb3norHoxd3,in the pharyngeal pouch endoderm.
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