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PMID:21703454

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Citation

Ezratty, EJ, Stokes, N, Chai, S, Shah, AS, Williams, SE and Fuchs, E (2011) A role for the primary cilium in Notch signaling and epidermal differentiation during skin development. Cell 145:1129-41

Abstract

Ciliogenesis precedes lineage-determining signaling in skin development. To understand why, we performed shRNA-mediated knockdown of seven intraflagellar transport proteins (IFTs) and conditional ablation of Ift-88 and Kif3a during embryogenesis. In both cultured keratinocytes and embryonic epidermis, all of these eliminated cilia, and many (not Kif3a) caused hyperproliferation. Surprisingly and independent of proliferation, ciliary mutants displayed defects in Notch signaling and commitment of progenitors to differentiate. Notch receptors and Notch-processing enzymes colocalized with cilia in wild-type epidermal cells. Moreover, differentiation defects in ciliary mutants were cell autonomous and rescued by activated Notch (NICD). By contrast, Shh signaling was neither operative nor required for epidermal ciliogenesis, Notch signaling, or differentiation. Rather, Shh signaling defects in ciliary mutants occurred later, arresting hair follicle morphogenesis in the skin. These findings unveil temporally and spatially distinct functions for primary cilia at the nexus of signaling, proliferation, and differentiation.

Links

PubMed PMC3135909 Online version:10.1016/j.cell.2011.05.030

Keywords

Animals; Carrier Proteins/genetics; Cell Differentiation; Cell Polarity; Cell Proliferation; Cilia/metabolism; Cytoskeletal Proteins/metabolism; Epidermis/cytology; Epidermis/embryology; Epidermis/metabolism; Gene Knockdown Techniques; Hair Follicle/cytology; Hedgehog Proteins/metabolism; Kinesis; Mice; Receptors, Notch/metabolism; Signal Transduction; Tumor Suppressor Proteins/metabolism

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