Endocrine - Parathyroid Development

Embryology - 16 Apr 2024        Expand to Translate
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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.

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.

| Lecture - Head Development |

Some Recent Findings

Human Embryo (week 6 - 8)

Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse "Hoxa3 was the first Hox gene to be mutated by gene targeting in mice and is required for the development of multiple endoderm and neural crest cell (NCC)-derived structures in the pharyngeal region. 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 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 "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

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Parathyroid Embryology <pubmed limit=5>Parathyroid Embryology</pubmed>

Development Overview

Parathyroid primordia (week 6 GA)

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

• chondrocyte differentiation

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

• 

  Parathyroid labeled (low power)

• 

  Parathyroid labeled (high power)

• 

  Parathyroid (low power)

• 

  Parathyroid (high power)

References

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

Search PubMed

Search April 2010

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

Search Pubmed: parathyroid development

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. (2024, April 16) Embryology Endocrine - Parathyroid Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Parathyroid_Development

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G