Building it up and taking it down: The regulation of vertebrate ciliogenesis

Santos, Nicole; Reiter, Jeremy F.

doi:10.1002/dvdy.21540

Cited by 109 publications

(97 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…29 Since CDK10/CycM has been previously linked to cell cycle regulation 30 it seems plausible that CDK10/CycM silencing might also contribute indirectly to ciliogenesis by promoting quiescence. Hence, we assessed the cell cycle status of siRNAtreated cells that were maintained in the presence of serum.…”

Section: Cdk10/cycm Negatively Regulates Ciliogenesis and Primary Cilmentioning

confidence: 99%

STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis

et al. 2016

View full text Add to dashboard Cite

CDK10/CycM is a protein kinase deficient in STAR (toe Syndactyly, Telecanthus and Anogenital and Renal malformations) syndrome, which results from mutations in the X-linked FAM58A gene encoding Cyclin M. The biological functions of CDK10/CycM and etiology of STAR syndrome are poorly understood. Here, we report that deficiency of CDK10/Cyclin M promotes assembly and elongation of primary cilia. We establish that this reflects a key role for CDK10/Cyclin M in regulation of actin network organization, which is known to govern ciliogenesis. In an unbiased screen, we identified the RhoA-associated kinase PKN2 as a CDK10/ CycM phosphorylation substrate. We establish that PKN2 is a bone fide regulator of ciliogenesis, acting in a similar manner to CDK10/CycM. We discovered that CDK10/Cyclin M binds and phosphorylates PKN2 on threonines 121 and 124, within PKN2 0 s core RhoA-binding domain. Furthermore, we demonstrate that deficiencies in CDK10/CycM or PKN2, or expression of a non-phosphorylatable version of PKN2, destabilize both the RhoA protein and the actin network architecture. Importantly, we established that ectopic expression of RhoA is sufficient to override the induction of ciliogenesis resulting from CDK10/CycM knockdown, indicating that RhoA regulation is critical for CDK10/CycM's negative effect on ciliogenesis. Finally, we show that kidney sections from a STAR patient display dilated renal tubules and abnormal, elongated cilia. Altogether, these results reveal CDK10/CycM as a key regulator of actin dynamics and a suppressor of ciliogenesis through phosphorylation of PKN2 and promotion of RhoA signaling. Moreover, they suggest that STAR syndrome is a ciliopathy.

show abstract

Section: Cdk10/cycm Negatively Regulates Ciliogenesis and Primary Cilmentioning

confidence: 99%

STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Primary cilia are regarded as postmitotic structures of quiescent cells (Santos and Reiter, 2008). Ciliary dynamics thus appears to be precisely coordinated with a cell cycle progression, but the molecular cues that trigger ciliogenesis at the node are poorly understood.…”

Section: Kip2mentioning

confidence: 99%

Cell cycle arrest in node cells governs ciliogenesis at the node to break left-right symmetry

2011

View full text Add to dashboard Cite

There was an error published in the ePress version of Development 138, 3915-3920 published on 10 August 2011.On p. 3919, in the legend for Fig. 4, asymmetry was incorrectly referred to as symmetry. The correct sentence appears in full below:Subsequently, nodal cilia develop and nodal flow is generated, which triggers the establishment of left-right asymmetry.The replacement ePress article published on 17 August 2011, the online issue and print copy are correct.We apologise to authors and readers for this error.

show abstract

“…Given that one of the centrioles of the centrosome forms the basal body of the primary cilium, this localizes the centrosomes of these cells to their apical plasma membrane. As the primary cilium is disassembled only shortly before the onset of mitosis (7), the nucleus, to undergo mitosis (in which the centrosomes serve as mitotic spindle poles), needs to be in the vicinity of the centrosomes, that is, at the apical surface. Thus, mitosis of these stem and progenitor cells occurs apically, and they will collectively be referred to as apical progenitors (APs).…”

mentioning

confidence: 99%

Myosin II is required for interkinetic nuclear migration of neural progenitors

Schenk

Wilsch‐Bräuninger

Calegari

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

149

151

View full text Add to dashboard Cite

Interkinetic nuclear migration (INM) is a hallmark of the polarized stem and progenitor cells in the ventricular zone (VZ) of the developing vertebrate CNS. INM is responsible for the pseudostratification of the VZ, a crucial aspect of brain evolution. The nuclear migration toward the apical centrosomes in G2 is thought to be a dyneinmicrotubule-based process. By contrast, the cytoskeletal machinery involved in the basally directed nuclear translocation away from the centrosome in G1 has been enigmatic. Studying the latter aspect of INM requires manipulation of the cytoskeleton without impairing mitosis and cytokinesis. To this end, we have established a culture system of mouse embryonic telencephalon that reproduces cortical development, and have applied it to explore a role of actomyosin in INM. Using the nonmuscle myosin II inhibitor blebbistatin at a low concentration at which neither cell cycle progression nor cytokinesis is impaired, we show that myosin II is required for the apical-to-basal (ap3bl), ab-centrosomal INM. Myosin II activity is also necessary for the nuclear translocation during delamination of subventricular zone (SVZ) cells, a second, telencephalon-specific type of neural progenitor. Moreover, the inhibition of ab-centrosomal INM changes the balance between VZ and SVZ progenitor cell fate. Our data suggest a unifying concept in which the actomyosin contraction underlying ab-centrosomal INM sets the stage for the evolutionary increase in VZ pseudostratification and for SVZ progenitor delamination, a key process in cortical expansion.cell cycle ͉ cerebral cortex ͉ cytoskeleton ͉ neural stem cells ͉ neurogenesis

show abstract

Building it up and taking it down: The regulation of vertebrate ciliogenesis

Cited by 109 publications

References 103 publications

STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis

STAR syndrome-associated CDK10/Cyclin M regulates actin network architecture and ciliogenesis

Cell cycle arrest in node cells governs ciliogenesis at the node to break left-right symmetry

Myosin II is required for interkinetic nuclear migration of neural progenitors

Contact Info

Product

Resources

About