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

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Abstract

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.

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Abbreviations

1,25-(OH)2D3 :

1,25-Dihydroxyvitamin D3

Bmp4:

Bone morphogenetic protein 4

BDNF:

Brain-derived neurotrophic factor

CaSR:

Calcium-sensing receptor

CGRP:

Calcitonin gene-related peptide

EGFR:

Epidermal growth factor receptor

Eya1:

Eyes absent 1

FGF:

Fibroblast growth factor

FGFR:

FGF receptor

Fox:

Forkhead box

Gcm2:

Glial cells missing 2

GFAP:

Glial fibrillary acidic protein

MafB:

V-Maf musculoaponeurotic fibrosarcoma oncogene homologue B

NGF:

Nerve growth factor

NT3:

Neurotrophin 3

NT4:

Neurotrophin 4

NTR:

Neurotrophin receptor

PGP9.5:

Protein gene product 9.5

PTH:

Parathormone

Sema3d:

Semaphorin 3d

Shh:

Sonic hedgehog

TH:

Tyrosine hydroxylase

VDR:

Vitamin D receptor

VIP:

Vasoactive intestinal polypeptide

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  1. Department of Anatomy, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan

    Yoko Kameda

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Kameda, Y. Cellular and molecular mechanisms of the organogenesis and development, and function of the mammalian parathyroid gland. Cell Tissue Res 393, 425–442 (2023). https://doi.org/10.1007/s00441-023-03785-3

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