Endocrine Abstracts

The four parathyroid glands (2 superior and 2 inferior) develop from the third and fourth branchial pouches. The 2 inferior parathyroids develop from the third branchial pouch, which also gives rise to the thymus, whilst the 2 superior parathyroids develop from the fourth branchial pouch. Recent molecular genetic studies have identified some of the genes (eg. GATA3, Gcm2 and Hoxa3) involved in these developmental pathways of the branchial pouches and parathyroids, and these will be reviewed. GATA3 haploinsufficiency has been shown to cause the human hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome, which may be inherited as an autosomal dominant syndrome. GATA3 belongs to a family of zinc-finger transcriptional factors that are involved in vertebrate embryonic development, and the HDR phenotype is consistent with the expression pattern of GATA3 during human and mouse embryogenesis in the developing kidney, otic vesicle and parathyroids. The homeobox gene, Hoxa3, has also been shown to be of importance in this pathway, as homozygous mutant knockout mice (-/-) lacking Hoxa3 have an absence of the thymus and parathyroids as well as a reduction in thyroid size, heart defects and craniofacial abnormalities. Homozygous mutant mice (-/-) that are deleted for Gcm2 (glial cells missing 2), which is the mouse homologue of the Drosphilia gene, Gcm, also lack parathyroids. However, these Gcm2 deficient mice had PTH concentrations identical to those of normal mice, indicating an auxillary source of PTH. This auxiliary source of PTH was found to be a cluster of PTH - expressing cells under the thymic capsule. Gcm2 has a role in human parathyroid development as a deletion in a patient has been reported to lead to hypoparathyroidism. These studies of hypoparathyroid patients and mouse models have helped to elucidate some of the genes involved in the embryological development of the parathyroids.