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Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation
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Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation
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Journal Article
Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation
2012
Overview
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.
Several specialized cell types assemble hundreds of motile cilia to accomplish their function. Kintner and colleagues identify the coiled-coil protein multicilin as an essential regulator of multicilia formation in
Xenopus
skin and the mammalian kidney. Their data indicate that multicilin activates the transcription of genes required for multicilia formation, including the transcription factor Foxj1.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Animals, Genetically Modified
/ Biomedical and Life Sciences
/ Cells
/ Embryo, Nonmammalian - cytology
/ Embryo, Nonmammalian - embryology
/ Embryo, Nonmammalian - metabolism
/ Embryos
/ Female
/ Females
/ Gene Expression Regulation, Developmental
/ Green Fluorescent Proteins - genetics
/ Green Fluorescent Proteins - metabolism
/ Humans
/ Kidneys
/ Male
/ Mice
/ Microscopy, Electron, Transmission
/ Proteins
/ Reverse Transcriptase Polymerase Chain Reaction
/ Sequence Homology, Amino Acid
/ Skin
/ Xenopus
