Universität zu Köln

Gozum, Gokcen ORCID: 0000-0002-8650-0078, Sharma, Lakshit, Henke, Paula, Wirtz, Lisa ORCID: 0000-0001-9967-6729, Damen, Mareike, Reckert, Viktoria, Schettina, Peter, Nelles, Melanie, Johnson, Craig N ORCID: 0000-0003-3955-7394, Bazzi, Hisham and Niemann, Catherin ORCID: 0000-0002-7224-6216 (2025). Specific and redundant roles for Gli2 and Gli3 in establishing cell fate during murine hair follicle development. The EMBO Journal, 44 (19). pp. 5290-5314. Springer Nature. ISSN 1460-2075

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Abstract

Formation of skin epithelial appendages like hair follicles requires hedgehog (Hh) signal reception, its conduction through the primary cilium and activation of Gli transcription factors. How Hh signalling induces cell-type-specific responses through Gli transcription fac- tors in hair follicle stem cells and their cilia-dependence remains unclear. Here, we use conditional mouse mutants to genetically dissect the roles of Gli2 and Gli3 transcription factors and cilia in the skin epithelium. Upon keratinocyte-specific depletion of Gli2, hair follicle morphogenesis is delayed whereas sebaceous gland formation is enhanced, suggesting a dual role for Gli2 during appendage development. Gli2 promotes proliferation of sebaceous gland stem cells, impacting the number and size of individual sebaceous gland lobes. While ablation of Gli3 shows no detectable phenotypes, hair follicle cell fate is blocked in Gli2/Gli3 double knockout (dKO) mice, suggesting functional compensation. Finally, loss of cilia phenocopies the depletion of Gli2 but not the Gli2/3 dKO mutants. Our study reveals compartment-specific regulation of murine skin morpohogenesis by Gli2 and cilia-independent activator functions of Gli3 in the absence of Gli2.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Gozum, Gokcen UNSPECIFIED https://orcid.org/0000-0002-8650-0078 UNSPECIFIED Sharma, Lakshit UNSPECIFIED UNSPECIFIED UNSPECIFIED Henke, Paula UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Lisa UNSPECIFIED https://orcid.org/0000-0001-9967-6729 UNSPECIFIED Damen, Mareike UNSPECIFIED UNSPECIFIED UNSPECIFIED Reckert, Viktoria UNSPECIFIED UNSPECIFIED UNSPECIFIED Schettina, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Nelles, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Johnson, Craig N UNSPECIFIED https://orcid.org/0000-0003-3955-7394 UNSPECIFIED Bazzi, Hisham UNSPECIFIED UNSPECIFIED UNSPECIFIED Niemann, Catherin UNSPECIFIED https://orcid.org/0000-0002-7224-6216 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-809872
Identification Number:	10.1038/s44318-025-00519-9
Journal or Publication Title:	The EMBO Journal
Volume:	44
Number:	19
Page Range:	pp. 5290-5314
Number of Pages:	25
Date:	26 August 2025
Publisher:	Springer Nature
ISSN:	1460-2075
Language:	English
Faculty:	Faculty of Medicine
Divisions:	CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Biochemie > Zentrum für Biochemie Faculty of Medicine > Dermatologie > Klinik und Poliklinik für Dermatologie und Venerologie Zentrum für Molekulare Medizin
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language Hedgehog ; Gli2 ; Hair Follicle ; Sebaceous Gland ; Stem Cell English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/80987