The Disruption of Sox21-mediated Hair Shaft Cuticle Differentiation Causes Cyclic Alopecia in Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 May 28

PMID 19470461

Citations 39

Authors

Makoto Kiso

Shigekazu Tanaka

Rie Saba

Satoru Matsuda

Atsushi Shimizu

Manabu Ohyama

Hirotaka James Okano

Toshihiko Shiroishi

Hideyuki Okano

Yumiko Saga

Affiliations

Soon will be listed here.

Abstract

Hair is maintained through a cyclic process that includes periodic regeneration of hair follicles in a stem cell-dependent manner. Little is known, however, about the cellular and molecular mechanisms that regulate the layered differentiation of the hair follicle. We have established a mutant mouse with a cyclic alopecia phenotype resulting from the targeted disruption of Sox21, a gene that encodes a HMG-box protein. These mice exhibit progressive hair loss after morphogenesis of the first hair follicle and become completely nude in appearance, but then show hair regrowth. Sox21 is expressed in the cuticle layer and the progenitor cells of the hair shaft in both mouse and human. The lack of this gene results in a loss of the interlocking structures required for anchoring the hair shaft in the hair follicle. Furthermore, the expression of genes encoding the keratins and keratin binding proteins in the hair shaft cuticle are also specifically down-regulated in the Sox21-null mouse. These results indicate that Sox21 is a master regulator of hair shaft cuticle differentiation and shed light on the possible causes of human hair disorders.

Citing Articles

Congenital microcoria deletion in mouse links Sox21 dysregulation to disease and suggests a role for TGFB2 in glaucoma and myopia.

Erjavec E, Angee C, Hadjadj D, Passet B, David P, Kostic C Am J Hum Genet. 2024; 111(10):2265-2282.

PMID: 39293448 PMC: 11480854. DOI: 10.1016/j.ajhg.2024.08.019.

Gene Misexpression in a +ve/-Low Population in Juvenile -Mutant Pituitary Gland.

Masser B, Brinkmeier M, Lin Y, Liu Q, Miyazaki A, Nayeem J J Endocr Soc. 2024; 8(10):bvae146.

PMID: 39253355 PMC: 11382140. DOI: 10.1210/jendso/bvae146.

In vitro induction of hair follicle signatures using human dermal papilla cells encapsulated in fibrin microgels.

Quilez C, Valencia L, Gonzalez-Rico J, Suarez-Cabrera L, Amigo-Moran L, Jorcano J Cell Prolif. 2023; 57(1):e13528.

PMID: 37539497 PMC: 10771113. DOI: 10.1111/cpr.13528.

Whole exome sequencing in Alopecia Areata identifies rare variants in KRT82.

Erjavec S, Gelfman S, Abdelaziz A, Lee E, Monga I, Alkelai A Nat Commun. 2022; 13(1):800.

PMID: 35145093 PMC: 8831607. DOI: 10.1038/s41467-022-28343-3.

SOX21 modulates SOX2-initiated differentiation of epithelial cells in the extrapulmonary airways.

Eenjes E, Buscop-van Kempen M, Boerema-de Munck A, Edel G, Benthem F, de Kreij-de Bruin L Elife. 2021; 10.

PMID: 34286693 PMC: 8331192. DOI: 10.7554/eLife.57325.

References

Reginelli A, Wang Y, Sassoon D, Muneoka K . Digit tip regeneration correlates with regions of Msx1 (Hox 7) expression in fetal and newborn mice. Development. 1995; 121(4):1065-76. DOI: 10.1242/dev.121.4.1065. View

Langbein L, Rogers M, Winter H, Praetzel S, Schweizer J . The catalog of human hair keratins. II. Expression of the six type II members in the hair follicle and the combined catalog of human type I and II keratins. J Biol Chem. 2001; 276(37):35123-32. DOI: 10.1074/jbc.M103305200. View

Fuchs E, Merrill B, Jamora C, Dasgupta R . At the roots of a never-ending cycle. Dev Cell. 2001; 1(1):13-25. DOI: 10.1016/s1534-5807(01)00022-3. View

Oshima H, Rochat A, Kedzia C, Kobayashi K, Barrandon Y . Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell. 2001; 104(2):233-45. DOI: 10.1016/s0092-8674(01)00208-2. View

Cotsarelis G, Sun T, Lavker R . Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990; 61(7):1329-37. DOI: 10.1016/0092-8674(90)90696-c. View

Rogers M, Langbein L, Praetzel-Wunder S, Winter H, Schweizer J . Human hair keratin-associated proteins (KAPs). Int Rev Cytol. 2006; 251:209-63. DOI: 10.1016/S0074-7696(06)51006-X. View

Stenn K, Paus R . Controls of hair follicle cycling. Physiol Rev. 2001; 81(1):449-494. DOI: 10.1152/physrev.2001.81.1.449. View

Uchikawa M, Kamachi Y, Kondoh H . Two distinct subgroups of Group B Sox genes for transcriptional activators and repressors: their expression during embryonic organogenesis of the chicken. Mech Dev. 1999; 84(1-2):103-20. DOI: 10.1016/s0925-4773(99)00083-0. View

Rogers G . Hair follicle differentiation and regulation. Int J Dev Biol. 2004; 48(2-3):163-70. View

10.

Price V, Gummer C . Loose anagen syndrome. J Am Acad Dermatol. 1989; 20(2 Pt 1):249-56. DOI: 10.1016/s0190-9622(89)70030-x. View

11.

Bowles J, Schepers G, Koopman P . Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators. Dev Biol. 2000; 227(2):239-55. DOI: 10.1006/dbio.2000.9883. View

12.

Legue E, Nicolas J . Hair follicle renewal: organization of stem cells in the matrix and the role of stereotyped lineages and behaviors. Development. 2005; 132(18):4143-54. DOI: 10.1242/dev.01975. View

13.

Tkatchenko A, Visconti R, Shang L, Papenbrock T, Pruett N, Ito T . Overexpression of Hoxc13 in differentiating keratinocytes results in downregulation of a novel hair keratin gene cluster and alopecia. Development. 2001; 128(9):1547-58. DOI: 10.1242/dev.128.9.1547. View

14.

Argenton F, Giudici S, Deflorian G, Cimbro S, Cotelli F, Beltrame M . Ectopic expression and knockdown of a zebrafish sox21 reveal its role as a transcriptional repressor in early development. Mech Dev. 2004; 121(2):131-42. DOI: 10.1016/j.mod.2004.01.001. View

15.

Muller-Rover S, Handjiski B, van der Veen C, Eichmuller S, Foitzik K, McKay I . A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol. 2001; 117(1):3-15. DOI: 10.1046/j.0022-202x.2001.01377.x. View

16.

Ohba H, Chiyoda T, Endo E, Yano M, Hayakawa Y, Sakaguchi M . Sox21 is a repressor of neuronal differentiation and is antagonized by YB-1. Neurosci Lett. 2004; 358(3):157-60. DOI: 10.1016/j.neulet.2004.01.026. View

17.

Sandberg M, Kallstrom M, Muhr J . Sox21 promotes the progression of vertebrate neurogenesis. Nat Neurosci. 2005; 8(8):995-1001. DOI: 10.1038/nn1493. View

18.

Langbein L, Rogers M, Winter H, Praetzel S, Beckhaus U, Rackwitz H . The catalog of human hair keratins. I. Expression of the nine type I members in the hair follicle. J Biol Chem. 1999; 274(28):19874-84. DOI: 10.1074/jbc.274.28.19874. View

19.

Ma L, Liu J, Wu T, Plikus M, Jiang T, Bi Q . 'Cyclic alopecia' in Msx2 mutants: defects in hair cycling and hair shaft differentiation. Development. 2002; 130(2):379-89. PMC: 4386654. DOI: 10.1242/dev.00201. View

20.

Johns S, Soullier S, Rashbass P, Cunliffe V . Foxn1 is required for tissue assembly and desmosomal cadherin expression in the hair shaft. Dev Dyn. 2005; 232(4):1062-8. DOI: 10.1002/dvdy.20278. View