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Signaling Involved in Hair Follicle Morphogenesis and Development
Department of Histology and Embryology, Medical Faculty in Hradec Kralove, Charles University in Prague, Simkova 870, 500 38 Hradec Kralove, Czech Republic
Department of Oncology and Radiotherapy, Medical Faculty in Hradec Kralove, Charles University in Prague, Simkova 870, 500 38 Hradec Kralove, Czech Republic
* Author to whom correspondence should be addressed.
Received: 10 August 2013; in revised form: 21 October 2013 / Accepted: 22 October 2013 / Published: 22 January 2014
Abstract: Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an essential role during hair follicle induction, Shh is involved in morphogenesis and late stage differentiation, Notch signaling determines stem cell fate while BMP is involved in cellular differentiation. The Wnt pathway is considered to be the master regulator during hair follicle morphogenesis. Wnt signaling proceeds through EDA/EDAR/NF-κB signaling. NF-κB regulates the Wnt pathway and acts as a signal mediator by upregulating the expression of Shh ligand. Signal crosstalk between epithelial and mesenchymal cells takes place mainly through primary cilia. Primary cilia formation is initiated with epithelial laminin-511 interaction with dermal β-1 integrin, which also upregulates expression of downstream effectors of Shh pathway in dermal lineage. PDGF signal transduction essential for crosstalk is mediated through epithelial PDGF-A and PDGFRα expressed on the primary cilia. Dermal Shh and PDGF signaling up-regulates dermal noggin expression; noggin is a potent inhibitor of BMP signaling which helps in counteracting BMP mediated β-catenin inhibition. This interplay of signaling between the epithelial and dermal lineage helps in epithelial Shh signal amplification. The dermal Wnt pathway helps in upregulation of epithelial Notch expression. Dysregulation of these pathways leads to certain abnormalities and in some cases even tumor outgrowth.
Keywords: hair follicle; morphogenesis; stem cell; signaling; Wnt; Shh; Notch; BMP
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Rishikaysh, P.; Dev, K.; Diaz, D.; Qureshi, W.M.S.; Filip, S.; Mokry, J. Signaling Involved in Hair Follicle Morphogenesis and Development. Int. J. Mol. Sci. 2014, 15, 1647-1670.
Rishikaysh P, Dev K, Diaz D, Qureshi WMS, Filip S, Mokry J. Signaling Involved in Hair Follicle Morphogenesis and Development. International Journal of Molecular Sciences. 2014; 15(1):1647-1670.
Rishikaysh, Pisal; Dev, Kapil; Diaz, Daniel; Qureshi, Wasay M.S.; Filip, Stanislav; Mokry, Jaroslav. 2014. "Signaling Involved in Hair Follicle Morphogenesis and Development." Int. J. Mol. Sci. 15, no. 1: 1647-1670.