Parafollicular cell explained

Parafollicular cell
Location:	Thyroid
Function:	Calcitonin secretion

Parafollicular cells, also called C cells, are neuroendocrine cells in the thyroid. They are called C cells because the primary function of these cells is to secrete calcitonin.^[1] They are located adjacent to the thyroid follicles and reside in the connective tissue. These cells are large and have a pale stain compared with the follicular cells. In teleost and avian species these cells occupy a structure outside the thyroid gland named the ultimopharyngeal body.

Structure

Parafollicular cells are pale-staining cells found in small number in the thyroid and are typically situated basally in the epithelium, without direct contact with the follicular lumen. They are always situated within the basement membrane, which surrounds the entire follicle.

Development

Parafollicular cells are derived from pharyngeal endoderm.^{[2] [3]} Embryologically, they associate with the ultimopharyngeal body, which is a ventral derivative of the fourth (or fifth) pharyngeal pouch. Parafollicular cells were previously believed to be derived from the neural crest based on a series of experiments in quail-chick chimeras.^{[4] [5]} However, lineage tracing experiments in mice revealed that parafollicular cells are derived from the endoderm origin.^[6]

Function

Parafollicular cells secrete calcitonin, a hormone that participates in the regulation of calcium metabolism. Calcitonin lowers blood levels of calcium by inhibiting the resorption of bone by osteoclasts, and its secretion is increased proportionally with the concentration of calcium.^[7]

Parafollicular cells are also known to secrete in smaller quantities several neuroendocrine peptides such as serotonin, somatostatin or CGRP.^{[8] [9] [10]} They may also have a role in regulating thyroid hormones production locally, as they express thyrotropin-releasing hormone.^{[11] [12]}

Clinical significance

When parafollicular cells become cancerous, they lead to medullary carcinoma of the thyroid.

See also

• List of human cell types derived from the germ layers
• List of distinct cell types in the adult human body

Further reading

• Kameda Y . Localization of immunoreactive calcitonin gene-related peptide in thyroid C cells from various mammalian species . The Anatomical Record . 219 . 2 . 204–12 . October 1987 . 3120623 . 10.1002/ar.1092190214 . 12517073 .
• Kameda Y, Nishimaki T, Miura M, Jiang SX, Guillemot F . Mash1 regulates the development of C cells in mouse thyroid glands . Developmental Dynamics . 236 . 1 . 262–70 . January 2007 . 17103415 . 10.1002/dvdy.21018 . 24848963 . free .
• Kameda Y, Nishimaki T, Chisaka O, Iseki S, Sucov HM . Expression of the epithelial marker E-cadherin by thyroid C cells and their precursors during murine development . The Journal of Histochemistry and Cytochemistry . 55 . 10 . 1075–88 . October 2007 . 17595340 . 10.1369/jhc.7a7179.2007 . free .
• Kameda Y, Ito M, Nishimaki T, Gotoh N . FRS2alpha is required for the separation, migration, and survival of pharyngeal-endoderm derived organs including thyroid, ultimobranchial body, parathyroid, and thymus . Developmental Dynamics . 238 . 3 . 503–13 . March 2009 . 19235715 . 10.1002/dvdy.21867 . 13504555 . free .
• Kameda Y . Cellular and molecular events on the development of mammalian thyroid C cells . Developmental Dynamics . 245 . 3 . 323–41 . March 2016 . 26661795 . 10.1002/dvdy.24377 . 12161896 . free .
• Contributions to the Minute Anatomy of the Thyroid Gland of the Dog . Baber EC . Philosophical Transactions of the Royal Society of London . 166 . 1876 . 557–568 . 109205 . 10.1098/rstl.1876.0021 .

Notes and References

1. Web site: Parafollicular Cell - an overview ScienceDirect Topics . 2024-02-03 . www.sciencedirect.com.
2. Nilsson M, Williams D . On the Origin of Cells and Derivation of Thyroid Cancer: C Cell Story Revisited . European Thyroid Journal . 5 . 2 . 79–93 . July 2016 . 27493881 . 4949372 . 10.1159/000447333 .
3. Johansson, E., Andersson, L., Örnros, J., Carlsson, T., Ingeson-Carlsson, C., Liang, S., … Nilsson, M. (2015). Revising the embryonic origin of thyroid C cells in mice and humans. Development, 142(20), 3519–3528. http://doi.org/10.1242/dev.126581
4. Le Douarin N, Fontaine J, Le Lièvre C . New studies on the neural crest origin of the avian ultimobranchial glandular cells--interspecific combinations and cytochemical characterization of C cells based on the uptake of biogenic amine precursors . Histochemistry . 38 . 4 . 297–305 . March 1974 . 4135055 . 10.1007/bf00496718 . 7551942 .
5. Barasch J, Gershon MD, Nunez EA, Tamir H, al-Awqati Q . Thyrotropin induces the acidification of the secretory granules of parafollicular cells by increasing the chloride conductance of the granular membrane . The Journal of Cell Biology . 107 . 6 Pt 1 . 2137–47 . December 1988 . 2461947 . 2115661 . 10.1083/jcb.107.6.2137 .
6. Johansson E, Andersson L, Örnros J, Carlsson T, Ingeson-Carlsson C, Liang S, Dahlberg J, Jansson S, Parrillo L, Zoppoli P, Barila GO, Altschuler DL, Padula D, Lickert H, Fagman H, Nilsson M . Revising the embryonic origin of thyroid C cells in mice and humans . Development . 142 . 20 . 3519–28 . October 2015 . 26395490 . 4631767 . 10.1242/dev.126581 .
7. Book: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM . Williams Textbook of Endocrinology . 2011 . Saunders . 1250–1252 . 978-1437703245 . 12th .
8. Zabel M . Ultrastructural localization of calcitonin, somatostatin and serotonin in parafollicular cells of rat thyroid . The Histochemical Journal . 16 . 12 . 1265–72 . December 1984 . 6152264 . 10.1007/bf01003725 . 7889687 .
9. Barasch JM, Mackey H, Tamir H, Nunez EA, Gershon MD . Induction of a neural phenotype in a serotonergic endocrine cell derived from the neural crest . The Journal of Neuroscience . 7 . 9 . 2874–83 . September 1987 . 3305802 . 10.1523/JNEUROSCI.07-09-02874.1987 . 6569149 .
10. Bernd P, Gershon MD, Nunez EA, Tamir H . Separation of dissociated thyroid follicular and parafollicular cells: association of serotonin binding protein with parafollicular cells . The Journal of Cell Biology . 88 . 3 . 499–508 . March 1981 . 7217200 . 2112761 . 10.1083/jcb.88.3.499 .
11. Gkonos PJ, Tavianini MA, Liu CC, Roos BA . Thyrotropin-releasing hormone gene expression in normal thyroid parafollicular cells . Molecular Endocrinology . 3 . 12 . 2101–9 . December 1989 . 2516877 . 10.1210/mend-3-12-2101 . free .
12. Morillo-Bernal J, Fernández-Santos JM, Utrilla JC, de Miguel M, García-Marín R, Martín-Lacave I . Functional expression of the thyrotropin receptor in C cells: new insights into their involvement in the hypothalamic-pituitary-thyroid axis . Journal of Anatomy . 215 . 2 . 150–8 . August 2009 . 19493188 . 2740962 . 10.1111/j.1469-7580.2009.01095.x .