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

2011; Nature Portfolio; Volume: 13; Issue: 4 Linguagem: Inglês

10.1038/ncb2183

1476-4679

Sehyun Kim, Norann A. Zaghloul, Ekaterina Bubenshchikova, Edwin C. Oh, Susannah Rankin, Nicholas Katsanis, Tomoko Obara, Leonidas Tsiokas,

Microtubule and mitosis dynamics

Ciliogenesis starts as cells enter quiescence and primary cilium resorption precedes mitosis. The centrosomal protein Nde1 is shown to regulate cilia length during the cell cycle. Loss of Nde1 in zebrafish leads to developmental patterning defects reflecting impaired control of cilium formation. 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.