TY - JOUR
T1 - Planar cell polarity effector gene Intu regulates cell fate-specific differentiation of keratinocytes through the primary cilia
AU - Dai, D.
AU - Li, L.
AU - Huebner, A.
AU - Zeng, H.
AU - Guevara, E.
AU - Claypool, D. J.
AU - Liu, A.
AU - Chen, J.
N1 - Funding Information:
Acknowledgements. We thank Dr. Dennis R Roop for helpful discussion, Christy Ou for assistance in statistical analyses and generating figures, Dorothy Dill (UCD EM Center) for assistance in transmission electron microscopy, Dr. Tamara Caspary for providing the Arl13b antibody, and Dr. Yutaka Shimomura for the KRT71 antibody. This study was supported in part by an International Union Against Cancer (UICC) and American Cancer Society Beginning Investigators Fellowship grant to LL; a Young Investigator Development Award from the PKD foundation to AL; a P&F grant and core services from the UCD Skin Disease Research Center (SDRC), and a research grant from NIH/NIAMS (AR061485) to JC.
PY - 2013/1
Y1 - 2013/1
N2 - Genes involved in the planar cell polarity (PCP) signaling pathway are essential for a number of developmental processes in mammals, such as convergent extension and ciliogenesis. Tissue-specific PCP effector genes of the PCP signaling pathway are believed to mediate PCP signals in a tissue-and cell type-specific manner. However, how PCP signaling controls the morphogenesis of mammalian tissues remains unclear. In this study, we investigated the role of inturned (Intu), a tissue-specific PCP effector gene, during hair follicle formation in mice. Tissue-specific disruption of Intu in embryonic epidermis resulted in hair follicle morphogenesis arrest because of the failure of follicular keratinocyte to differentiate. Targeting Intu in the epidermis resulted in almost complete loss of primary cilia in epidermal and follicular keratinocytes, and a suppressed hedgehog signaling pathway. Surprisingly, the epidermal stratification and differentiation programs and barrier function were not affected. These results demonstrate that tissue-specific PCP effector genes of the PCP signaling pathway control the differentiation of keratinocytes through the primary cilia in a cell fate-and context-dependent manner, which may be critical in orchestrating the propagation and interpretation of polarity signals established by the core PCP components.
AB - Genes involved in the planar cell polarity (PCP) signaling pathway are essential for a number of developmental processes in mammals, such as convergent extension and ciliogenesis. Tissue-specific PCP effector genes of the PCP signaling pathway are believed to mediate PCP signals in a tissue-and cell type-specific manner. However, how PCP signaling controls the morphogenesis of mammalian tissues remains unclear. In this study, we investigated the role of inturned (Intu), a tissue-specific PCP effector gene, during hair follicle formation in mice. Tissue-specific disruption of Intu in embryonic epidermis resulted in hair follicle morphogenesis arrest because of the failure of follicular keratinocyte to differentiate. Targeting Intu in the epidermis resulted in almost complete loss of primary cilia in epidermal and follicular keratinocytes, and a suppressed hedgehog signaling pathway. Surprisingly, the epidermal stratification and differentiation programs and barrier function were not affected. These results demonstrate that tissue-specific PCP effector genes of the PCP signaling pathway control the differentiation of keratinocytes through the primary cilia in a cell fate-and context-dependent manner, which may be critical in orchestrating the propagation and interpretation of polarity signals established by the core PCP components.
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U2 - 10.1038/cdd.2012.104
DO - 10.1038/cdd.2012.104
M3 - Article
C2 - 22935613
AN - SCOPUS:84871006384
SN - 1350-9047
VL - 20
SP - 130
EP - 138
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 1
ER -