Hox genes in the pharyngeal region: how Hoxa3 controls early embryonic development of the pharyngeal organs

Abstract

The pharyngeal organs, namely the thyroid, thymus, parathyroids, and ultimobranchial bodies, derive from the pharyngeal endoderm during embryonic development. The pharyngeal region is a segmented structure comprised of a series of reiterated structures: the pharyngeal arches on the exterior surface, the pharyngeal pouches on the interior, and a mesenchymal core. It is well known that Hox genes control spatial identity along the anterior-posterior axis of the developing vertebrate embryo, and nowhere is this is more evident than in the pharyngeal region. Each of the distinct segmented regions has a unique pattern of Hox expression, which conveys crucial positional information to the cells and tissues within it. In the context of pharyngeal organ development, molecular data suggest that HOXA3 is responsible for specifying organ identity within the third pharyngeal pouch, and in its absence, thymus and parathyroid organogenesis fails to proceed normally. Recent studies comprising a series of Hoxa3 mutations identified specific spatial and temporal roles for HOXA3 in pharyngeal organ development, including both cell-autonomous and non-autonomous functions, revealing a system that is more complex than originally thought. Here, we will review the current understanding of the role of Hox genes in the early embryonic development of the pharyngeal organs in the mouse, with a particular focus on the function of HOXA3 in thymus and parathyroid organogenesis.