Endocrine - Parathyroid Development

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Introduction

Embryonic origins of the endocrine organs of the neck

The parathyroid gland appears in the adult as a pair of inferior and a pair of superior "bumps" on the beside the (dorsal) thyroid (hence the name, "para"). The embryonic origin of this gland is from the third and fourth pharyngeal pouches endoderm, and could also have ectoderm and neural crest contributions. This developmental process also generates multiple small parathyroid clusters in addition to the main parathyroid glands.[1]


At 6 weeks a diverticulum elongates from the pouch, initially hollow and then solidifynig with cell proliferation.


Interestingly, the inferior parathyroid originates from the third pharyngeal pouch and the superior arises from the fourth pharyngeal pouch, the adult anatomical position is the opposite of the pharyngeal rostro-caudal order. This occurs due to the third pharyngeal pouch also giving rise to the thymus, the superior pair descend along with the thymus.


The fetal parathyroids appear functional as they respond to calcium levels. The fetal calcium levels also higher than maternal levels.


Endocrine Links: Introduction | BGD Lecture | Science Lecture | Lecture Movie | Pineal | Hypothalamus‎ | Pituitary | Thyroid | Parathyroid | Thymus‎ | Pancreas‎ | Adrenal‎ | Gonad‎ | Placenta‎ | Other Tissues | Stage 22 | Abnormalities | Hormones | Category:Endocrine
Historic Embryology - Endocrine  
1903 Islets of Langerhans | 1904 interstitial Cells | 1908 Pancreas Different Species | 1908 Pituitary | 1908 Pituitary histology | 1911 Rathke's pouch | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1915 Pharynx | 1916 Thyroid | 1918 Rabbit Hypophysis | 1920 Adrenal | 1935 Mammalian Hypophysis | 1926 Human Hypophysis | 1927 Hypophyseal fossa | 1935 Hypophysis | 1937 Pineal | 1938 Parathyroid | 1940 Adrenal | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus | 1957 Adrenal

Historically, see also the 1938 paper on the fate of the ultimobranchial body within the human thyroid gland.[2]

Some Recent Findings

Human Embryo (week 6 - 8)[1]
  • Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse[3] "Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. Expression of the parathyroid marker Gcm2 was initiated but was quickly downregulated and differentiation failed; by contrast, thymus markers were delayed but achieved normal levels, concurrent with complete loss through apoptosis. To determine the cell type-specific roles of Hoxa3 in third pharyngeal pouch development, we analyzed tissue-specific mutants using endoderm and/or neural crest cell (NCC)-specific Cre drivers. Simultaneous deletion with both drivers resulted in athymia at E18.5, similar to the null. By contrast, the individual tissue-specific Hoxa3 deletions resulted in small, ectopic thymi, although each had a unique phenotype. Hoxa3 was primarily required in NCCs for morphogenesis. In endoderm, Hoxa3 temporally regulated initiation of the thymus program and was required in a cell-autonomous manner for parathyroid differentiation. Furthermore, Hoxa3 was required for survival of third pharyngeal pouch-derived organs, but expression in either tissue was sufficient for this function." Developmental Signals - Homeobox
  • Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions[1] "In mammals, parathyroid hormone (PTH) is a key regulator of extracellular calcium and inorganic phosphorus homeostasis. Although the parathyroid glands were thought to be the only source of PTH, extra-parathyroid PTH production in the thymus, which shares a common origin with parathyroids during organogenesis, has been proposed to provide an auxiliary source of PTH, resulting in a higher than expected survival rate for aparathyroid Gcm2⁻/⁻ mutants. However, the developmental ontogeny and cellular identity of these "thymic" PTH-expressing cells is unknown. ...Our data show conclusively that the thymus does not serve as an auxiliary source of either serum PTH or parathyroid function. We further show that the normal process of parathyroid organogenesis in both mice and humans leads to the generation of multiple small parathyroid clusters in addition to the main parathyroid glands, that are the likely source of physiologically relevant "thymic PTH."" Endocrine - Thymus Development
More recent papers  
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Search term: Parathyroid Embryology

Naoki Morito, Keigyou Yoh, Toshiaki Usui, Hisashi Oishi, Masami Ojima, Akiko Fujita, Ryusuke Koshida, Hossam H Shawki, Michito Hamada, Masafumi Muratani, Kunihiro Yamagata, Satoru Takahashi Transcription factor MafB may play an important role in secondary hyperparathyroidism. Kidney Int.: 2017; PubMed 28964572

Barbara Gellén, Dóra Zelena, Ted B Usdin, Árpád Dobolyi The parathyroid hormone 2 receptor participates in physiological and behavioral alterations of mother mice. Physiol. Behav.: 2017; PubMed 28890271

Petr Libánský, Svatopluk Adámek, Petr Broulík, Martina Fialová, Josef Kubinyi, Robert Lischke, Ondřej Naňka, Pavel Pafko, Jiří Šedý, Vladimír Bobek Parathyroid Carcinoma in Patients that Have Undergone Surgery for Primary Hyperparathyroidism. In Vivo: 2017, 31(5);925-930 PubMed 28882960

S Jia, J Zhou, Y Wee, M L Mikkola, P Schneider, R N D'Souza Anti-EDAR Agonist Antibody Therapy Resolves Palate Defects in Pax9(-/-) Mice. J. Dent. Res.: 2017;22034517726073 PubMed 28813171

Berthold Hocher, Andreas Pasch Hope for CKD-MBD Patients: New Diagnostic Approaches for Better Treatment of CKD-MBD. Kidney Dis (Basel): 2017, 3(1);8-14 PubMed 28785559

Development Overview

Parathyroid primordia (week 6 GA)[1]
Adult parathyroid anatomy
  • Endoderm - third and fourth pharyngeal pouches, could also have ectoderm and neural crest
  • 3rd Pharyngeal Pouch - inferior parathyroid, initially descends with thymus
  • 4th Pharyngeal Pouch - superior parathyroid
  • Week 6 - diverticulum elongate, hollow then solid, dorsal cell proliferation
  • Fetal parathyroids - respond to calcium levels, fetal calcium levels higher than maternal

Parathyroid Hormone

(PTH, parathormone or parathyrin) A polypeptide (84 amino acids) hormone which increases the concentration of calcium ions in the blood. Its actions oppose the hormone calcitonin from the thyroid gland parafollicular cells (C cells), which decrease calcium. Acts through the parathyroid hormone receptor in bone, kidney and gastrointestinal tract.

  • stimulate osteoclasts - degrade bone matrix, releasing calcium
  • increase calcium gastrointestinal tract absorption

Parathyroid Hormone-related Protein

(PTHrP) Originally identified in the clinical syndrome humoral hypercalcemia of malignancy. It's developmental role is that of a regulatory protein expressed during the formation of many organs.

  • mammary gland development - epithelial-mesenchymal interactions[4]
  • chondrocyte differentiation[5]

Abnormalities

Hyperparathyroidism

Postnatal

  • Postnatal adult ageing increased parathyroid hormone plasma levels are associated with cognitive decline and dementia.
  • Parathyroid carcinoma (cancer) is a rare malignancy, occurring with an incidence of 0.5 to 4% of all cases of primary hyperparathyroidism.

Adult Histology

References

  1. 1.0 1.1 1.2 1.3 Zhijie Liu, Alison Farley, Lizhen Chen, Beth J Kirby, Christopher S Kovacs, C Clare Blackburn, Nancy R Manley Thymus-associated parathyroid hormone has two cellular origins with distinct endocrine and immunological functions. PLoS Genet.: 2010, 6(12);e1001251 PubMed 21203493 Cite error: Invalid <ref> tag; name "PMID21203493" defined multiple times with different content Cite error: Invalid <ref> tag; name "PMID21203493" defined multiple times with different content Cite error: Invalid <ref> tag; name "PMID21203493" defined multiple times with different content
  2. Kingsbury BF. On the fate of the ultimobranchial body within the human thyroid gland. (1935) Anat. Rec. 61(2): 155–173.
  3. Jena L Chojnowski, Kyoko Masuda, Heidi A Trau, Kirk Thomas, Mario Capecchi, Nancy R Manley Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse. Development: 2014, 141(19);3697-708 PubMed 25249461
  4. M E Dunbar, J J Wysolmerski Parathyroid hormone-related protein: a developmental regulatory molecule necessary for mammary gland development. J Mammary Gland Biol Neoplasia: 1999, 4(1);21-34 PubMed 10219904
  5. Benjamin A Alman, Jay S Wunder Parathyroid hormone-related protein regulates glioma-associated oncogene transcriptional activation: lessons learned from bone development and cartilage neoplasia. Ann. N. Y. Acad. Sci.: 2008, 1144;36-41 PubMed 19076361


Reviews

  • The development of the parathyroid gland: from fish to human. Zajac JD, Danks JA. Curr Opin Nephrol Hypertens. 2008 Jul;17(4):353-6. Review. PMID: 18660669
  • Parathyroid development and the role of tubulin chaperone E. Parvari R, Diaz GA, Hershkovitz E. Horm Res. 2007;67(1):12-21. Epub 2006 Sep 27. Review. PMID: 17008776
  • Role of parathyroid hormone-related peptide and Indian hedgehog in skeletal development. Jüppner H. Pediatr Nephrol. 2000 Jul;14(7):606-11. Review. PMID: 10912527

Articles

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  • Parathyroid Development - All (3523) Review (768) Free Full Text (741)


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Terms

  • parathyroid hormone - (PTH, parathormone or parathyrin) A polypeptide (84 amino acids) hormone secreted by the parathyroid gland, which increases the concentration of calcium ions in the blood. Its actions oppose the hormone calcitonin from the thyroid gland parafollicular cells (C cells), which decrease calcium. Acts through the parathyroid hormone receptor located mainly in bone, kidney and gastrointestinal tract. Hormone dual role is to: stimulate osteoclasts in bone to degrade bone matrix releasing calcium; increase gastrointestinal tract absorption of calcium.


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Cite this page: Hill, M.A. 2017 Embryology Endocrine - Parathyroid Development. Retrieved November 22, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Parathyroid_Development

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© Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G