During neural tube closure, regulated changes at the level of individual cells are translated into large-scale morphogenetic movements to facilitate conversion of the flat neural plate into a closed tube. Throughout this process, the integrity of the neural epithelium is maintained via cell interactions through intercellular junctions, including apical tight junctions. Members of the claudin family of tight junction proteins regulate paracellular permeability, apical-basal cell polarity and link the tight junction to the actin cytoskeleton. Here, we show that claudins are essential for neural tube closure: the simultaneous removal of Cldn3, −4 and −8 from tight junctions caused folate-resistant open neural tube defects. Their removal did not affect cell type differentiation, neural ectoderm patterning nor overall apical-basal polarity. However, apical accumulation of Vangl2, RhoA, and pMLC were reduced, and Par3 and Cdc42 were mislocalized at the apical cell surface. Our data showed that claudins act upstream of planar cell polarity and RhoA/ROCK signaling to regulate cell intercalation and actin-myosin contraction, which are required for convergent extension and apical constriction during neural tube closure, respectively.

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BACKGROUND Croup is a self-limiting illness predominantly affecting young children, the most common etiology being Parainfluenza virus types 1 and 2. While the majority of croup remains self-limiting, 1.6–3% of cases are severe requiring acute airway management such as intubation and ventilatory support. While much is known about the diagnosis, management, and clinical course of self-limiting croup, factors contributing to severe cases remain unexplored. OBJECTIVES To characterize the clinical features and risk factors associated with severe croup in children admitted to a tertiary care centre. DESIGN/METHODS A retrospective chart review study of paediatric patients with severe croup presenting at a single tertiary care paediatric institution between 2011 and 2015 was performed. Severe croup was defined as those requiring major airway intervention (i.e. intubation), emergent management in the operating room (i.e. rigid bronchoscopy) or admission to the paediatric intensive care unit. Our findings were compared to previous reported characteristics of children with viral croup and recurrent croup. Multiple univariate regression models were constructed to isolate predictor variables of longer hospital stay and isolate confounders such as known comorbidities and risk factors. RESULTS Sixty-seven croup patients were analyzed, aged 4–170 months (median, 15) of which 76.8% were male. Several presented with risk factors, namely previous croup history (23.2%), intubation history (13%), airway abnormalities (8.7%) and nonspecific reactive airway disease (8.7%), while others exhibited comorbid conditions such as asthma (7.3%), GERD (14.5%) and known drug allergy (5.8%). In our cohort, Parainfluenza virus type 3 (PIV3) was shown to be a predictor for increased length of stay with a univariate regression coefficient of 3.2 (95% CI 0.72–5.7). Known croup risk factors did not contribute to the effect observed with PIV3 (coefficient 3.0, 95% CI 0.4–5.7). Further analysis accounting for comorbidity confounders predicted a coefficient of 2.6 for PIV3 (95% CI 0.01–5.12). Mean length of stay for PIV3 infected children was 7.4 nights. CONCLUSION To our knowledge, this is the first study linking PIV3 with severe croup and predicting longer hospitalizations in this cohort. Further investigation is required to determine optimal management of PIV3-infected croup patients to shorten clinical course and improve patient outcomes.

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