Centrioles are ancient organelles that build centrosomes, the major microtubule-organizing centers of animal cells. Extra centrosomes are a common feature of cancer cells. To investigate the importance of centrosomes in the proliferation of normal and cancer cells, we developed centrinone, a reversible inhibitor of Polo-like kinase 4 (Plk4), a serine-threonine protein kinase that initiates centriole assembly. Centrinone treatment caused centrosome depletion in human and other vertebrate cells. Centrosome loss irreversibly arrested normal cells in a senescence-like G1 state by a p53-dependent mechanism that was independent of DNA damage, stress, Hippo signaling, extended mitotic duration, or segregation errors. In contrast, cancer cell lines with normal or amplified centrosome numbers could proliferate indefinitely after centrosome loss. Upon centrinone washout, each cancer cell line returned to an intrinsic centrosome number “set point.” Thus, cells with cancer-associated mutations fundamentally differ from normal cells in their response to centrosome loss.

The planar cell polarity (PCP) signaling system governs many aspects of polarized cell behavior. Here, we use an in vivo model of vertebrate mucociliary epithelial development to show that Dishevelled (Dvl) is essential for the apical positioning of basal bodies. We find that Dvl and Inturned mediate the activation of the Rho GTPase specifically at basal bodies, and that these three proteins together mediate the docking of basal bodies to the apical plasma membrane. Moreover, we find that the docking involves a Dvl-dependent association of basal bodies with membrane-bound vesicles and with the vesicle-trafficking protein, Sec8. Once docked, Dvl and Rho are once again required for the planar polarization of basal bodies that underlies directional beating of cilia. These results demonstrate novel functions for PCP signaling components and suggest that a common signaling appratus governs both apical docking and planar polarization of basal bodies.

Actin dynamics are required for proper cilia spacing, global coordination of cilia polarity, and coordination of metachronic cilia beating, whereas cytoplasmic microtubule dynamics are required for local coordination of polarity between neighboring cilia.

Regional variations of the intrinsic shear wave quality factor Qµ in both the upper crust and upper mantle of continents are large, with values in old, stable cratons exceeding those in tectonically active regions in both depth ranges by as much as an order of magnitude or more. Qµ depends upon frequency, at least near 1 Hz, and that frequency dependence also varies regionally in the upper crust. It is typically low in tectonically active regions and higher in stable regions. Because of the large variations in Qµ from region to region, it is easy to map regional variations of both upper crustal Qµ and Q estimated from the coda of Lg waves (QLgc), even though both measurements may be marked by large uncertainties. Although coda Q of direct body waves may be strongly affected by scattering, QLgc appears to be primarily governed by intrinsic Qµ in the upper crust. Both upper crustal Qµ and QLgc values correlate with the time that has elapsed since the most recent tectonic activity in continental regions. A tomographic image of the variation of QLgc values across Africa shows reduced Q values which correspond to recent tectonic activity in the East African rift system and other regions of Mesozoic or younger age. Reductions of QLgc that correlate with tectonic activity that occurred in the early Paleozoic during the coalescence of the cratons which formed that continent can also be detected. Qµ increases rapidly at midcrustal depths, in a range which appears to coincide with the transition to the plastic lower crust. In the lower crust and upper mantle, Qµ decreases with increasing depth, possibly by progressive unpinning of dislocations with increasing temperature. Observed regional variations in upper mantle Qµ at depths of about 150 km can be explained by differences in temperature alone, but those at crustal depths cannot. Regional variations of Qµ in the upper crust are most easily explained by differences in the density of fluid‐filled fractures in which fluids can move during the propagation of seismic waves. Studies of the regional variation of Qµ and QLgc indicate that crack density is greatest during and immediately following tectonic activity in a region and that it decreases with time. Permeability determinations in deep wells show that fluid movements in those cracks may be largely restricted to zones of crustal fracturing. That situation will produce widely differing values of Q in local studies, depending on the location of the study relative to the fractures. The fluid volume in cracks appears to decrease with time by loss to the surface or by retrograde metamorphism, causing a reduction in the number of open cracks and a concomitant increase in Qµ.

Ciliated epithelia produce fluid flow in many organ systems, ranging from the respiratory tract where it clears mucus to the ventricles of the brain where it transports cerebrospinal fluid. Human diseases that disable ciliary flow, such as primary ciliary dyskinesia, can compromise organ function or the ability to resist pathogens, resulting in recurring respiratory infections, otitis, hydrocephaly and infertility. To create a ciliary flow, the cilia within each cell need to be polarized coordinately along the planar axis of the epithelium, but how polarity is established in any ciliated epithelia is not known. Here we analyse the developmental mechanisms that polarize cilia, using the ciliated cells in the developing Xenopus larval skin as a model system. We show that cilia acquire polarity through a sequence of events, beginning with a polar bias set by tissue patterning, followed by a refinement phase. Our results indicate that during refinement, fluid flow is both necessary and sufficient in determining cilia polarity. These findings reveal a novel mechanism in which tissue patterning coupled with fluid flow act in a positive feedback loop to direct the planar polarity of cilia.