Cellular and molecular mechanisms of the organogenesis and development, and function of the mammalian parathyroid gland.

Serum calcium homeostasis is mainly regulated by parathormone (PTH) secreted by the parathyroid gland. Besides PTH and Gcm2, a master gene for parathyroid differentiation, many genes are expressed in the gland. Especially, calcium-sensing receptor (CaSR), vitamin D receptor (VDR), and Klotho function to prevent increased secretion of PTH and hyperplasia of the parathyroid gland under chronic hypocalcemia. Parathyroid-specific dual deletion of Klotho and CaSR induces a marked enlargement of the glandular size. The parathyroid develops from the third and fourth pharyngeal pouches except murine species in which the gland is derived from the third pouch only. The development of the murine parathyroid gland is categorized as follows: (1) formation and differentiation of the pharyngeal pouches, (2) appearance of parathyroid domain in the third pharyngeal pouch together with thymus domain, (3) migration of parathyroid primordium attached to the top of thymus, and (4) contact with the thyroid lobe and separation from the thymus. The transcription factors and signaling molecules involved in each of these developmental stages are elaborated. In addition, mesenchymal neural crest cells surrounding the pharyngeal pouches and parathyroid primordium and invading the parathyroid parenchyma participate in the development of the gland.