Differential role of planar cell polarity gene Vangl2 in embryonic and adult mammalian kidneys.

Planar cell polarity (PCP) pathway is crucial for tissue morphogenesis. Mutations in PCP genes cause multi-organ anomalies including dysplastic kidneys. Defective PCP signaling was postulated to contribute to cystogenesis in polycystic kidney disease. This work was undertaken to elucidate the role of the key PCP gene, Vangl2, in embryonic and postnatal renal tubules and ascertain whether its loss contributes to cyst formation and defective tubular function in mature animals. We generated mice with ubiquitous and collecting duct-restricted excision of Vangl2. We analyzed renal tubules in mutant and control mice at embryonic day E17.5 and postnatal days P1, P7, P30, P90, 6- and 9-month old animals. The collecting duct functions were analyzed in young and adult mutant and control mice. Loss of Vangl2 leads to profound tubular dilatation and microcysts in embryonic kidneys. Mechanistically, these abnormalities are caused by defective convergent extension (larger tubular cross-sectional area) and apical constriction (cuboidal cell shape and a reduction of activated actomyosin at the luminal surface). However, the embryonic tubule defects were rapidly resolved by Vangl2-independent mechanisms after birth. Normal collecting duct architecture and functions were found in young and mature animals. During embryogenesis, Vangl2 controls tubular size via convergent extension and apical constriction. However, rapidly after birth, PCP-dependent control of tubular size is switched to a PCP-independent regulatory mechanism. We conclude that loss of the Vangl2 gene is dispensable for tubular elongation and maintenance postnatally. It does not lead to cyst formation and is unlikely to contribute to polycystic kidney disease.

The Effect of Bariatric Surgery on Migraines: a Systematic Review and Meta-analysis.

INTRODUCTION: Recent research has demonstrated an association between obesity and migraine headaches. Furthermore, studies have demonstrated that migraine improvement can occur with significant weight loss. Given that bariatric surgery is the most effective intervention for obesity and obesity-related comorbidities, there is potential for bariatric surgery to improve migraine symptoms. The objective of this study was to conduct a systematic review and meta-analysis to determine the effect of bariatric surgery on migraine headaches. METHODS: A comprehensive literature search from database inception to December 2018 was conducted for studies examining the effect of bariatric surgery on migraines. Patients of all ages who had a history of migraines undergoing primary bariatric surgery were included. Primary outcomes included migraine frequency, severity, and disability. RESULTS: Four studies were included (n = 159). Frequency of migraines was markedly reduced after bariatric surgery, with fewer symptomatic days suffered by patients per month post-operatively (mean difference [MD] - 5.56 days, 95%CI 0.14 to 10.99, p = 0.04). The degree of migraine headache-related disability as measured by the Migraine Disability Assessment Scale (MIDAS) was also significantly lower following bariatric surgery (MD - 14.72, 95%CI 10.08 to 19.36, p < 0.001). The severity of migraine headache pain before and after surgery was reduced with borderline statistical significance (MD - 3.53, 95%CI - 0.12 to 7.17, p = 0.06). CONCLUSION: Migraine severity, frequency, and headache-related disability were improved 6 months after bariatric surgery. However, this systematic review was limited by a low number of studies and larger high-quality, randomized trials are needed to determine the effect of bariatric surgery on migraine headaches.