Beyond Cell Cycle Control

Science Signaling  04 Jan 2011:
Vol. 4, Issue 154, pp. ec4
DOI: 10.1126/scisignal.4154ec4

Members of the Cdc14 family of phosphatases promote mitotic exit by reversing phosphorylation events catalyzed by cyclin-dependent kinase 1 (Cdk1) and are essential for cell cycle progression in some species but dispensable in others. Clément et al. report that Cdc14B is required for ciliogenesis, independent of its role in cell cycle regulation. Embryos injected with antisense morpholino oligonucleotides targeting cdc14b displayed phenotypes consistent with aberrant ciliogenesis, including kidney cysts, hydrocephaly, and left-right patterning defects (randomization of gut and heart looping and of pancreas and liver positioning). The earliest marker of left-right asymmetry was abnormal, which suggests a defect in Kupffer’s vesicle (KV), an early embryonic structure in which beating cilia establish asymmetric fluid flow that, in turn, defines left-right asymmetry throughout the embryo. KV development and cell number were normal in cdc14b morphants, but the cilia were shorter, and fluid flow was disrupted. Left-right asymmetry defects were rescued by injection of wild-type cdc14b mRNA but not mRNA encoding a phosphatase-dead version of Cdc14b. Cilia in the kidney ducts were present in normal numbers but shorter, and the ducts were enlarged, consistent with defective fluid flow. Cilia in the inner ear were also shortened; in addition, the number of cilia-bearing cells was reduced because of decreased proliferation of progenitor cells, which indicated that the cilia and cell cycle roles of Cdc14b are separable. Initiation of cilium formation occurred normally in morphant kidney duct cells, which implied that the defect lay in elongation. Cdc14b affected cilium elongation independently of fibroblast growth factor (FGF) signaling, a known regulator of cilium length. Although the mechanism of Cdc14b regulation of cilium length remains to be elucidated, the authors suggest that this phosphatase likely affects cilium length by regulating microtubule dynamics. It is unclear whether this role in ciliogenesis is specific to fish or shared with other species, but the multifunctionality of Cdc14s may account for some of the variability in requirements for these phosphatases across species.

A. Clément, L. Solnica-Krezel, K. L. Gould, The Cdc14B phosphatase contributes to ciliogenesis in zebrafish. Development 138, 291–302 (2011). [Abstract] [Full Text]