Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry

Nat Cell Biol. 2011 Apr;13(4):351-60. doi: 10.1038/ncb2183. Epub 2011 Mar 13.

Abstract

The primary cilium is an antenna-like organelle that is dynamically regulated during the cell cycle. Ciliogenesis is initiated as cells enter quiescence, whereas resorption of the cilium precedes mitosis. The mechanisms coordinating ciliogenesis with the cell cycle are unknown. Here we identify the centrosomal protein Nde1 (nuclear distribution gene E homologue 1) as a negative regulator of ciliary length. Nde1 is expressed at high levels in mitosis, low levels in quiescence and localizes at the mother centriole, which nucleates the primary cilium. Cells depleted of Nde1 have longer cilia and a delay in cell cycle re-entry that correlates with ciliary length. Knockdown of Nde1 in zebrafish embryos results in increased ciliary length, suppression of cell division, reduction of the number of cells forming the Kupffer's vesicle and left-right patterning defects. These data suggest that Nde1 is an integral component of a network coordinating ciliary length with cell cycle progression and have implications for understanding the transition from a quiescent to a proliferative state.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cilia / physiology*
  • Cilia / ultrastructure
  • Cytoplasmic Dyneins / genetics
  • Cytoplasmic Dyneins / metabolism
  • Mice
  • Microtubule-Associated Proteins
  • Morphogenesis / physiology*
  • NIH 3T3 Cells
  • Zebrafish / anatomy & histology
  • Zebrafish / embryology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Nde1 protein, mouse
  • Zebrafish Proteins
  • Cytoplasmic Dyneins