No abstract

SUMMARY During cell division, polarized epithelial cells employ mechanisms to preserve cell polarity and tissue integrity. In dividing cells of the mammalian skin, planar cell polarity (PCP) is maintained through the bulk internalization, equal segregation, and polarized recycling of cortical PCP proteins. The dramatic redistribution of PCP proteins coincides precisely with cell cycle progression, but the mechanisms coordinating PCP and mitosis are unknown. Here we identify Plk1 as a master regulator of PCP dynamics during mitosis. Plk1 interacts with core PCP component, Celsr1, via a conserved polo-box domain (PBD) binding motif, localizes to mitotic endosomes and directly phosphorylates Celsr1. Plk1-dependent phosphorylation activates the endocytic motif specifically during mitosis, allowing bulk recruitment of Celsr1 into endosomes. Inhibiting Plk1 activity blocks PCP internalization and perturbs PCP asymmetry. Mimicking dileucine motif phosphorylation is sufficient to drive Celsr1 internalization during interphase. Thus, Plk1-mediated phosphorylation of Celsr1 ensures PCP redistribution is precisely coordinated with mitotic entry.

A group of Hanuman langurs (Presbytis entellus) was studied before and after it was moved from an old cage-style enclosure to a novel naturalistic environment at the London Zoo. Eating and locomotion occupied more of the langurs' time in their new enclosure, whereas dozing, allogrooming, and aggression decreased, along with an increase in inter-individual distances. These changes are attributed to the larger area, the stimulating new environment, and the langurs' increased distance from visitors. Nevertheless, the study raises questions about how to define standards of desirable environmental enrichment, as the activity patterns recorded in both the old and new enclosures are within the variation observed in the wild.

The skin microbiome provides vital contributions to human health and was historically assumed to be a well-mixed community that coats the skin surface. However, its spatial organization and viability remain unclear. Here we apply culturing, imaging, and molecular approaches to both human and mouse skin samples, and find that the skin surface is colonized by far few viable bacteria than would be predicted by its levels of bacterial DNA. Instead, viable skin-associated bacteria are primarily present in hair follicles and other cutaneous invaginations. Furthermore, we establish that a relatively small number of bacterial families dominate each skin site and that traditional sequencing methods overestimate the skin microbiome's richness and diversity. These findings address multiple outstanding questions in skin microbiome biology with significant implications for future efforts to study and manipulate it.

Cadherin EGF LAG seven-pass G-type receptor (Celsr) proteins 1-3 comprise a subgroup of adhesion GPCRs whose functions range from planar cell polarity (PCP) signaling to axon pathfinding and ciliogenesis. Like its Drosophila ortholog, Flamingo, mammalian Celsr1 is a core component of the PCP pathway, which, among other roles, is responsible for the coordinated alignment of hair follicles across the skin surface. Although the role of Celsr1 in epidermal planar polarity is well established, the contribution of the other major epidermally expressed Celsr protein, Celsr2, has not been investigated. Here, using two new CRISPR/Cas9-targeted Celsr1 and Celsr2 knockout mouse lines, we define the relative contributions of Celsr1 and Celsr2 to PCP establishment in the skin. We find that Celsr1 is the major Celsr family member involved in epidermal PCP. Removal of Celsr1 function alone abolishes PCP protein asymmetry and hair follicle polarization, whereas epidermal PCP is unaffected by loss of Celsr2. Further, elimination of both Celsr proteins only minimally enhances the Celsr1−/− phenotype. Using FRAP and junctional enrichment assays to measure differences in Celsr1 and Celsr2 adhesive interactions, we find that compared to Celsr1, which stably enriches at junctional interfaces, Celsr2 is much less efficiently recruited to and immobilized at junctions. As the two proteins seem equivalent in their ability to interact with core PCP proteins Vangl2 and Fz6, we suggest that perhaps differences in homophilic adhesion contribute to the differential involvement of Celsr1 and Celsr2 in epidermal PCP.