Role of epidermal primary cilia in the homeostasis of skin and hair follicles

Croyle, Mandy J.; Lehman, Jonathan M.; O’Connor, Amber K.; Wong, Sunny Y.; Malarkey, Erik B.; Iribarne, Daniela; Dowdle, William E.; Schoeb, Trenton R.; Verney, Zoe M.; Athar, Mohammad; Michaud, Edward J.; Reiter, Jeremy F.; Yoder, Bradley K.

doi:10.1242/jcs.091256

Cited by 19 publications

(47 citation statements)

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“…Two recent studies 64,65 have recently reported that impaired ciliogenesis impacts skin homeostasis and affects the pilosebaceous unit from which cylindroma are believed to originate. This convinced us that future studies designed to precisely characterize the molecular pathways regulated by CYLD during ciliogenesis might provide novel insights into how CYLD deregulation results in cylindroma in the cylindromatosis pathology.…”

Section: Discussionmentioning

confidence: 99%

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

et al. 2014

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CYLD is a tumour suppressor gene mutated in familial cylindromatosis, a genetic disorder leading to the development of skin appendage tumours. It encodes a deubiquitinating enzyme that removes Lys63-or linear-linked ubiquitin chains. CYLD was shown to regulate cell proliferation, cell survival and inflammatory responses, through various signalling pathways. Here we show that CYLD localizes at centrosomes and basal bodies via interaction with the centrosomal protein CAP350 and demonstrate that CYLD must be both at the centrosome and catalytically active to promote ciliogenesis independently of NF-kB. In transgenic mice engineered to mimic the smallest truncation found in cylindromatosis patients, CYLD interaction with CAP350 is lost disrupting CYLD centrosome localization, which results in cilia formation defects due to impairment of basal body migration and docking. These results point to an undiscovered regulation of ciliogenesis by Lys63 ubiquitination and provide new perspectives regarding CYLD function that should be considered in the context of cylindromatosis.

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Section: Discussionmentioning

confidence: 99%

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

et al. 2014

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“…Deletion of Kif3a or Itf88, critical for cilia formation, results in hyperproliferative skin lesions and excessive migration of bulge SCs to the IFE (Croyle et al 2011). Human BCCs are also ciliated, and deletion of Kif3a or Itf88 blocked SmoM2-induced tumorigenesis but enhanced Gli2-mediated BCC formation (Wong et al 2009), suggesting that cilia can either potentiate or inhibit tumorigenesis depending on the oncogenic context.…”

Section: Regulation Of Skin Stem Cellsmentioning

confidence: 99%

Development and Homeostasis of the Skin Epidermis

Sotiropoulou

Blanpain

2012

Cold Spring Harbor Perspectives in Biology

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SUMMARYThe skin epidermis is a stratified epithelium that forms a barrier that protects animals from dehydration, mechanical stress, and infections. The epidermis encompasses different appendages, such as the hair follicle (HF), the sebaceous gland (SG), the sweat gland, and the touch dome, that are essential for thermoregulation, sensing the environment, and influencing social behavior. The epidermis undergoes a constant turnover and distinct stem cells (SCs) are responsible for the homeostasis of the different epidermal compartments. Deregulation of the signaling pathways controlling the balance between renewal and differentiation often leads to cancer formation.

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“…The analysis of this issue is complicated, however, because kinesin-II mouse knock-outs (KOs) lead to midgestation lethality (12,13). Consequently, conditional KOs of Kif3a have been performed in several organs, including kidney tubules, pancreas, and skin, and in all cases resulted in a loss of cilia, demonstrating that Kif3a is necessary for ciliogenesis (14)(15)(16). As the vertebrate photoreceptor outer segment is among the best characterized cilia-derived structures (17,18), several studies focused on the role of kinesins in photoreceptor ciliogenesis.…”

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confidence: 99%

Kinesin-2 family in vertebrate ciliogenesis

Zhao

Omori²,

Brodowska

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

124

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The differentiation of cilia is mediated by kinesin-driven transport. As the function of kinesins in vertebrate ciliogenesis is poorly characterized, we decided to determine the role of kinesin-2 family motors-heterotrimeric kinesin-II and the homodimeric Kif17 kinesin-in zebrafish cilia. We report that kif17 is largely dispensable for ciliogenesis; kif17 homozygous mutant animals are viable and display subtle morphological defects of olfactory cilia only. In contrast to that, the kif3b gene, encoding a heterotrimeric kinesin subunit, is necessary for cilia differentiation in most tissues, although exceptions exist, and include photoreceptors and a subset of hair cells. Cilia of these cell types persist even in kif3b/kif17 double mutants. Although we have not observed a functional redundancy of kif3b and kif17, kif17 is able to substitute for kif3b in some cilia. In contrast to kif3b/kif17 double mutants, simultaneous interference with kif3b and kif3c leads to the complete loss of photoreceptor and hair cell cilia, revealing redundancy of function. This is in agreement with the idea that Kif3b and Kif3c motor subunits form complexes with Kif3a, but not with each other. Interestingly, kif3b mutant photoreceptor cilia differentiate with a delay, suggesting that kif3c, although redundant with kif3b at later stages of differentiation, is not active early in photoreceptor ciliogenesis. Consistent with that, the overexpression of kif3c in kif3b mutants rescues early photoreceptor cilia defects. These data reveal unexpected diversity of functional relationships between vertebrate ciliary kinesins, and show that the repertoire of kinesin motors changes in some cilia during their differentiation. intraflagellar transport | opsin | outer segment | ciliary axoneme

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Role of epidermal primary cilia in the homeostasis of skin and hair follicles

Cited by 19 publications

References 1 publication

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells

Development and Homeostasis of the Skin Epidermis

Kinesin-2 family in vertebrate ciliogenesis

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