View source for Parafollicular cell

{{Short description|Neuroendocrine cells in the thyroid}}
{{Infobox cell
| Name        = Parafollicular cell
| Latin       =
| Image       = Tiroides 03 100X.JPG
| Caption     = Microscopic section of the thyroid showing follicles lined by follicular epithelial cells, and in between them larger parafollicular cells.
| Image2      =
| Caption2    =
| Precursor   =
| System      =
| Location = [[Thyroid]]
| Function = [[Calcitonin]] secretion
}}
'''Parafollicular cells''', also called '''C cells''', are [[neuroendocrine cell]]s in the [[thyroid]]. They are called C cells because the primary function of these cells is to secrete [[calcitonin]].<ref>{{Cite web |title=Parafollicular Cell - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/parafollicular-cell#:~:text=Structure%20and%20Function,are%20present%20in%20parafollicular%20positions. |access-date=2024-02-03 |website=www.sciencedirect.com}}</ref> 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 [[Thyroid epithelial cell|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]].<ref>{{cite journal | vauthors = Nilsson M, Williams D | title = On the Origin of Cells and Derivation of Thyroid Cancer: C Cell Story Revisited | journal = European Thyroid Journal | volume = 5 | issue = 2 | pages = 79–93 | date = July 2016 | pmid = 27493881 | pmc = 4949372 | doi = 10.1159/000447333 }}</ref><ref>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</ref> Embryologically, they associate with the [[ultimopharyngeal body]], which is a ventral derivative of the fourth (or fifth) [[pharyngeal pouch (embryology)|pharyngeal pouch]]. Parafollicular cells were previously believed to be derived from the [[neural crest]] based on a series of experiments in quail-chick chimeras.<ref>{{cite journal | vauthors = Le Douarin N, Fontaine J, Le Lièvre C | title = 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 | journal = Histochemistry | volume = 38 | issue = 4 | pages = 297–305 | date = March 1974 | pmid = 4135055 | doi = 10.1007/bf00496718 | s2cid = 7551942 }}</ref><ref>{{cite journal | vauthors = Barasch J, Gershon MD, Nunez EA, Tamir H, al-Awqati Q | title = Thyrotropin induces the acidification of the secretory granules of parafollicular cells by increasing the chloride conductance of the granular membrane | journal = The Journal of Cell Biology | volume = 107 | issue = 6 Pt 1 | pages = 2137–47 | date = December 1988 | pmid = 2461947 | pmc = 2115661 | doi = 10.1083/jcb.107.6.2137 }}</ref> However, lineage tracing experiments in mice revealed that parafollicular cells are derived from the endoderm origin.<ref>{{cite journal | vauthors = 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 | title = Revising the embryonic origin of thyroid C cells in mice and humans | journal = Development | volume = 142 | issue = 20 | pages = 3519–28 | date = October 2015 | pmid = 26395490 | pmc = 4631767 | doi = 10.1242/dev.126581 }}</ref>

== Function ==
Parafollicular cells secrete [[calcitonin]], a hormone that participates in the regulation of [[calcium metabolism]]. Calcitonin lowers blood levels of calcium by inhibiting the [[bone resorption|resorption of bone]] by [[osteoclast]]s, and its secretion is increased proportionally with the concentration of calcium.<ref name=williams>{{cite book | vauthors = Melmed S, Polonsky KS, Larsen PR, Kronenberg HM | title = Williams Textbook of Endocrinology | date = 2011 | publisher = Saunders | pages = 1250–1252 | isbn = 978-1437703245 | edition = 12th }}</ref>

Parafollicular cells are also known to secrete in smaller quantities several neuroendocrine peptides such as [[serotonin]], [[somatostatin]] or [[CGRP]].<ref>{{cite journal | vauthors = Zabel M | title = Ultrastructural localization of calcitonin, somatostatin and serotonin in parafollicular cells of rat thyroid | journal = The Histochemical Journal | volume = 16 | issue = 12 | pages = 1265–72 | date = December 1984 | pmid = 6152264 | doi = 10.1007/bf01003725 | s2cid = 7889687 }}</ref><ref>{{cite journal | vauthors = Barasch JM, Mackey H, Tamir H, Nunez EA, Gershon MD | title = Induction of a neural phenotype in a serotonergic endocrine cell derived from the neural crest | journal = The Journal of Neuroscience | volume = 7 | issue = 9 | pages = 2874–83 | date = September 1987 | pmid = 3305802 | url= | doi = 10.1523/JNEUROSCI.07-09-02874.1987 | pmc = 6569149 }}</ref><ref>{{cite journal | vauthors = Bernd P, Gershon MD, Nunez EA, Tamir H | title = Separation of dissociated thyroid follicular and parafollicular cells: association of serotonin binding protein with parafollicular cells | journal = The Journal of Cell Biology | volume = 88 | issue = 3 | pages = 499–508 | date = March 1981 | pmid = 7217200 | pmc = 2112761 | doi = 10.1083/jcb.88.3.499 }}</ref>  They may also have a role in regulating thyroid hormones production locally, as they express [[thyrotropin-releasing hormone]].<ref>{{cite journal | vauthors = Gkonos PJ, Tavianini MA, Liu CC, Roos BA | title = Thyrotropin-releasing hormone gene expression in normal thyroid parafollicular cells | journal = Molecular Endocrinology | volume = 3 | issue = 12 | pages = 2101–9 | date = December 1989 | pmid = 2516877 | doi = 10.1210/mend-3-12-2101 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Morillo-Bernal J, Fernández-Santos JM, Utrilla JC, de Miguel M, García-Marín R, Martín-Lacave I | title = Functional expression of the thyrotropin receptor in C cells: new insights into their involvement in the hypothalamic-pituitary-thyroid axis | journal = Journal of Anatomy | volume = 215 | issue = 2 | pages = 150–8 | date = August 2009 | pmid = 19493188 | pmc = 2740962 | doi = 10.1111/j.1469-7580.2009.01095.x }}</ref>

==Clinical significance==
When parafollicular cells become cancerous, they lead to [[medullary thyroid cancer|medullary carcinoma]] of the thyroid.{{Citation needed|date=May 2021}}

== See also ==
*[[List of human cell types derived from the germ layers]]
*[[List of distinct cell types in the adult human body]]

== References ==
{{Reflist|32em}}

== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = Kameda Y | title = Localization of immunoreactive calcitonin gene-related peptide in thyroid C cells from various mammalian species | journal = The Anatomical Record | volume = 219 | issue = 2 | pages = 204–12 | date = October 1987 | pmid = 3120623 | doi = 10.1002/ar.1092190214 | s2cid = 12517073 }}
* {{cite journal | vauthors = Kameda Y, Nishimaki T, Miura M, Jiang SX, Guillemot F | title = Mash1 regulates the development of C cells in mouse thyroid glands | journal = Developmental Dynamics | volume = 236 | issue = 1 | pages = 262–70 | date = January 2007 | pmid = 17103415 | doi = 10.1002/dvdy.21018 | s2cid = 24848963 | doi-access = free }}
* {{cite journal | vauthors = Kameda Y, Nishimaki T, Chisaka O, Iseki S, Sucov HM | title = Expression of the epithelial marker E-cadherin by thyroid C cells and their precursors during murine development | journal = The Journal of Histochemistry and Cytochemistry | volume = 55 | issue = 10 | pages = 1075–88 | date = October 2007 | pmid = 17595340 | doi = 10.1369/jhc.7a7179.2007 | doi-access = free }}
* {{cite journal | vauthors = Kameda Y, Ito M, Nishimaki T, Gotoh N | title = FRS2alpha is required for the separation, migration, and survival of pharyngeal-endoderm derived organs including thyroid, ultimobranchial body, parathyroid, and thymus | journal = Developmental Dynamics | volume = 238 | issue = 3 | pages = 503–13 | date = March 2009 | pmid = 19235715 | doi = 10.1002/dvdy.21867 | s2cid = 13504555 | doi-access = free }}
* {{cite journal | vauthors = Kameda Y | title = Cellular and molecular events on the development of mammalian thyroid C cells | journal = Developmental Dynamics | volume = 245 | issue = 3 | pages = 323–41 | date = March 2016 | pmid = 26661795 | doi = 10.1002/dvdy.24377 | s2cid = 12161896 | doi-access = free }}
* {{cite journal | title = Contributions to the Minute Anatomy of the Thyroid Gland of the Dog | vauthors = Baber EC | journal = Philosophical Transactions of the Royal Society of London | volume = 166 | year = 1876 | pages = 557–568 | jstor = 109205 | doi = 10.1098/rstl.1876.0021 | doi-access =  }}
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== External links ==
* {{OklahomaHistology|42_04}}
* {{BUHistology|14302loa}}
* {{KansasHistology|endo|/endo10}} 
* {{AnatomyAtlasesMicroscopic|15|287}}

{{Endocrine system}}
{{Authority control}}

[[Category:Endocrine system anatomy]]
[[Category:Peptide hormone secreting cells]]
[[Category:Human cells]]
[[Category:Thyroid]]