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XB-ART-44680
Nat Cell Biol. January 29, 2012; 14 (2): 140-7.

Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation.

Stubbs JL , Vladar EK , Axelrod JD , Kintner C .


Abstract
Multiciliate cells function prominently in the respiratory system, brain ependyma and female reproductive tract to produce vigorous fluid flow along epithelial surfaces. These specialized cells form during development when epithelial progenitors undergo an unusual form of ciliogenesis, in which they assemble and project hundreds of motile cilia. Notch inhibits multiciliate cell formation in diverse epithelia, but how progenitors overcome lateral inhibition and initiate multiciliate cell differentiation is unknown. Here we identify a coiled-coil protein, termed multicilin, which is regulated by Notch and highly expressed in developing epithelia where multiciliate cells form. Inhibiting multicilin function specifically blocks multiciliate cell formation in Xenopus skin and kidney, whereas ectopic expression induces the differentiation of multiciliate cells in ectopic locations. Multicilin localizes to the nucleus, where it directly activates the expression of genes required for multiciliate cell formation, including foxj1 and genes mediating centriole assembly. Multicilin is also necessary and sufficient to promote multiciliate cell differentiation in mouse airway epithelial cultures. These findings indicate that multicilin initiates multiciliate cell differentiation in diverse tissues, by coordinately promoting the transcriptional changes required for motile ciliogenesis and centriole assembly.

PubMed ID: 22231168
PMC ID: PMC3329891
Article link: Nat Cell Biol.
Grant support: R01 GM059823 NIGMS NIH HHS , R01 GM059823-12 NIGMS NIH HHS , R01 GM096021 NIGMS NIH HHS , R01 GM098582-02 NIGMS NIH HHS , R01 GM096021-01 NIGMS NIH HHS , R01 GM098582 NIGMS NIH HHS , T32 CA009151 NCI NIH HHS , R01 GM096021 NIGMS NIH HHS , R01 GM098582 NIGMS NIH HHS , T32 CA009151 NCI NIH HHS , R01 GM059823 NIGMS NIH HHS , R01 GM096021-01 NIGMS NIH HHS

Genes referenced: cdh1 foxj1 foxj1.2 gal.2 mcc myc notch1 odc1 pcnt tjp1 tspan31

Morpholinos referenced: foxj1 MO1

References:
Amaya, 1999, Pubmed, Xenbase[+]


Article Images: [+] show captions

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