The ciliopathy gene Rpgrip1l is essential for hair follicle development.
The primary cilium is essential for skin morphogenesis through regulating the Notch, Wnt, and hedgehog signaling pathways. Prior studies on the functions of primary cilia in the skin were based on the investigations of genes that are essential for cilium formation. However, none of these ciliogenic genes has been linked to ciliopathy, a group of disorders caused by abnormal formation or function of cilia. To determine whether there is a genetic and molecular link between ciliopathies and skin morphogenesis, we investigated the role of RPGRIP1L, a gene mutated in Joubert (JBTS) and Meckel (MKS) syndromes, two severe forms of ciliopathy, in the context of skin development. We found that RPGRIP1L is essential for hair follicle morphogenesis. Specifically, disrupting the Rpgrip1l gene in mice resulted in reduced proliferation and differentiation of follicular keratinocytes, leading to hair follicle developmental defects. These defects were associated with significantly decreased primary cilium formation and attenuated hedgehog signaling. In contrast, we found that hair follicle induction and polarization and the development of interfollicular epidermis were unaffected. This study indicates that RPGRIP1L, a ciliopathy gene, is essential for hair follicle morphogenesis likely through regulating primary cilia formation and the hedgehog signaling pathway.
Department of Pathology, Stony Brook University, Stony Brook, New York, USA; Department of Dermatology, Stony Brook University, Stony Brook, New York, USA. Electronic address: jiang.chen@stonybrook.edu.
Jiang
J
Chen
IBPS-Developmental Biology Laboratory, Centre National de la Recherche Scientifique (CNRS) UMR 7622, Paris, France; UMR7622, UPMC Univ Paris 06, Sorbonne-Université, Paris, France.
Christine
C
Laclef
Department of Pathology, Stony Brook University, Stony Brook, New York, USA.
Alejandra
A
Moncayo
Department of Pathology, Stony Brook University, Stony Brook, New York, USA; Graduate Program in Genetics, Stony Brook University, Stony Brook, New York, USA.
Elizabeth R
ER
Snedecor
Department of Pathology, Stony Brook University, Stony Brook, New York, USA.
Ning
N
Yang
Department of Dermatology, Peking Union Medical College Hospital, Beijing, China.
Li
L
Li
Department of Pharmacology, Stony Brook University, Stony Brook, New York, USA.
Ken-Ichi
KI
Takemaru
Dermatology Research Centre, Institute of Inflammation and Repair, University of Manchester, Manchester, UK; Department of Dermatology, University of Münster, Münster, Germany.
Ralf
R
Paus
IBPS-Developmental Biology Laboratory, Centre National de la Recherche Scientifique (CNRS) UMR 7622, Paris, France; UMR7622, UPMC Univ Paris 06, Sorbonne-Université, Paris, France.
Sylvie
S
Schneider-Maunoury
Department of Dermatology, Stony Brook University, Stony Brook, New York, USA.
Richard A
RA
Clark
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology*; D018859:Hair Follicle / Q000254:growth & development* / Q000502:physiology*; D053823:Hedgehog Proteins / Q000502:physiology; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D023421:Models, Animal; D009024:Morphogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000254:growth & development
D048868:Adaptor Proteins, Signal Transducing; C523257:Ftm protein, mouse; D053823:Hedgehog Proteins