After wounding, a G-protein coupled receptor promotes the restoration of tension in epithelial cells.

The maintenance of epithelial barrier function involves cellular tension, with cells pulling on their neighbors to maintain epithelial integrity. Wounding interrupts cellular tension, which may serve as an early signal to initiate epithelial repair. To characterize how wounds alter cellular tension we used a laser-recoil assay to map cortical tension around wounds in the epithelial monolayer of the Drosophila pupal notum. Within a minute of wounding, there was widespread loss of cortical tension along both radial and tangential directions. This tension loss was similar to levels observed with Rok inactivation. Tension was subsequently restored around the wound, first in distal cells and then in proximal cells, reaching the wound margin ∼10 min after wounding. Restoring tension required the GPCR Mthl10 and the IP3 receptor, indicating the importance of this calcium signaling pathway known to be activated by cellular damage. Tension restoration correlated with an inward-moving contractile wave that has been previously reported; however, the contractile wave itself was not affected by Mthl10 knockdown. These results indicate that cells may transiently increase tension and contract in the absence of Mthl10 signaling, but that pathway is critical for fully resetting baseline epithelial tension after it is disrupted by wounding.

High-throughput gene expression analysis identifies p53-dependent and -independent pathways contributing to the adrenocortical dysplasia (acd) phenotype.

In mammalian cells TPP1, encoded by the Acd gene, is a key component of the shelterin complex, which is required for telomere length maintenance and telomere protection. In mice, a hypomorphic mutation in Acd causes the adrenocortical dysplasia (acd) phenotype, which includes limb and body axis anomalies, and perinatal lethality. p53 deficiency partially rescues limb and body axis anomalies in acd mutant embryos, but not perinatal lethality, implicating p53-independent mechanisms in the acd phenotype. Loss of function of most shelterin proteins results in early embryonic lethality. Thus, study of the hypomorphic acd allele provides a unique opportunity to understand telomere dysfunction at an organismal level. The aim of this study was to identify transcriptome alterations in acd mutant and acd, p53 double mutant embryos to understand the p53-dependent and -independent factors that contribute to the mutant phenotypes in the context of the whole organism. Genes involved in developmental processes, cell cycle, metabolic pathways, tight junctions, axon guidance and signaling pathways were regulated by p53-driven mechanisms in acd mutant embryos, while genes functioning in immune response, and RNA processing were altered independently of p53 in acd, p53 double mutant embryos. To our best of knowledge, this is the first study revealing detailed transcriptomic alterations, reflecting novel p53-dependent and -independent pathways contributing to the acd phenotype. Our data confirm the importance of cell cycle and DNA repair pathways, and suggest novel links between telomere dysfunction and immune system regulation and the splicing machinery. Given the broad applicability of telomere maintenance in growth, development, and genome stability, our data will also provide a rich resource for others studying telomere maintenance and DNA damage responses in mammalian model systems.

Surgical management and outcome of lower eyelid entropion in 124 cats.

OBJECTIVES: To evaluate the success rate of various surgical techniques for the management of lower eyelid entropion in cats. DESIGN: Retrospective study. Animals studied One hundred and twenty-four cats with surgical correction of lower eyelid entropion of 200 eyes over a 13 year period. METHODS: Records of 124 cats were reviewed for signalment, type of entropion, surgical procedure performed and post-operative result. RESULTS: Combinations of the Hotz-Celsus (HC), lateral canthal closure and full thickness wedge resection techniques were used to treat 64 bilateral and 60 unilateral cases of lower lid entropion. Twenty-three cats were under a year of age, 52 cats were aged between 2 and 8 years and 49 were over 8 years old. The overall success rate for a single surgical procedure (which may consist of multiple techniques) to correct lower eyelid entropion was 96.0% per eye. The remaining 4.0% had the entropion resolved with a second surgery. A combined HC and lateral canthal closure had a 99.21% success rate of resolving lower lid entropion. Geriatric cats were the most likely age group to develop corneal sequestra; 37% of cats in this group presented with entropion and corneal sequestra concurrently. Seventeen percent of cats that presented with unilateral entropion and did not have prophylactic surgery on the fellow eye went on to develop entropion in the fellow eye. CONCLUSIONS: A combined HC and lateral canthal closure was the most effective surgical technique in managing lower eyelid entropion of cats in our study. Prophylactic lateral canthal closure in the unaffected eye is recommended.