Multicilin Promotes Centriole Assembly and Ciliogenesis During Multiciliate Cell Differentiation

Nat Cell Biol. 2012 Jan 8;14(2):140-7. doi: 10.1038/ncb2406.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation*
  • Cell Nucleus / metabolism
  • Centrioles / physiology*
  • Cilia / physiology*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Female
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • In Situ Hybridization
  • Kidney / cytology
  • Kidney / embryology
  • Kidney / metabolism
  • Male
  • Mice
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Skin / cytology
  • Skin / embryology
  • Skin / metabolism
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Xenopus Proteins / physiology*
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism

Substances

  • Xenopus Proteins
  • multicilin, Xenopus
  • Green Fluorescent Proteins

Associated data

  • GEO/GSE32331