Control of tissue morphology by Fasciclin III-mediated intercellular adhesion.

Morphogenesis is dependent on the orchestration of multiple developmental processes to generate mature functional organs. However, the signalling pathways that coordinate morphogenesis and the mechanisms that translate these signals into tissue shape changes are not well understood. Here, we demonstrate that changes in intercellular adhesion mediated by the transmembrane protein Fasciclin III (FasIII) represent a key mediator of morphogenesis. Using the embryonic Drosophila hindgut as an in vivo model for organogenesis, we show that the tightening of hindgut curvature that normally occurs between embryonic stage 12 and 15 to generate the characteristic shepherd's crook shape is dependent on localised JAK/STAT pathway activation. This localised pathway activity drives the expression of FasIII leading to its subcellular lateralisation at a stage before formation of septate junctions. Additionally, we show that JAK/STAT- and FasIII-dependent morphogenesis also regulates folds within the third instar wing imaginal disc. We show that FasIII forms homophilic intercellular interactions that promote intercellular adhesion in vivo and in cultured cells. To explore these findings, we have developed a mathematical model of the developing hindgut, based on the differential interfacial tension hypothesis (DITH) linking intercellular adhesion and localised surface tension. Our model suggests that increased intercellular adhesion provided by FasIII can be sufficient to drive the tightening of tube curvature observed. Taken together, these results identify a conserved molecular mechanism that directly links JAK/STAT pathway signalling to intercellular adhesion and that sculpts both tubular and planar epithelial shape.

Factors associated with emergency department visits in asthma exacerbation.

OBJECTIVES: Despite quality improvement initiatives to prevent asthma-related emergency department (ED) visits, rates have not declined. We sought to determine factors associated with ED visits in an underserved population. METHODS: We performed a case-control analysis of asthma patients at three ambulatory care centers serving low-income populations. Cases consisted of asthmatic patients aged 18 to 45 years with ≥1 ED visit for an asthma exacerbation between August 1, 2008 and July 31, 2010. Controls were patients with asthma aged 18 to 45 years with ≥1 outpatient visit during the same period but with no asthma-related ED visit. Data were collected by chart review and included demographics, past referral for asthma education or to a pulmonologist, recent tobacco use, influenza vaccination, and asthma medication prescriptions in the year before the index visit. RESULTS: Among 244 cases and 475 controls, there were no significant differences in age, sex, or ethnicity. Cases were more likely than controls to have ever been referred for asthma education (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.57-6.50) or to a pulmonologist (OR 2.31, 95% CI 1.15-4.66). In the year before the index visit, cases were more likely than controls to receive other medications in addition to inhaled corticosteroids (ICS; OR 1.74, 95% CI 1.14-2.66) but less likely to receive influenza vaccination (OR 0.49, 95% CI 0.34-0.71), a short-acting ß-agonist (OR 0.43, 95% CI 0.24-0.78), or ICS alone (OR 0.53, 95% CI 0.34-0.84). CONCLUSIONS: Markers of severe disease were associated with ED visits, as well as a lack of an influenza vaccination and failure to prescribe either ICS or short-acting ß-agonists.

Localised JAK/STAT pathway activation is required for Drosophila wing hinge development.

Extensive morphogenetic remodelling takes place during metamorphosis from a larval to an adult insect body plan. These changes are particularly intricate in the generation of the dipteran wing hinge, a complex structure that is derived from an apparently simple region of the wing imaginal disc. Using the characterisation of original outstretched alleles of the unpaired locus as a starting point, we demonstrate the role of JAK/STAT pathway signalling in the process of wing hinge development. We show that differences in JAK/STAT signalling within the proximal most of three lateral folds present in the wing imaginal disc is required for fold morphology and the subsequent differentiation of the first and second auxiliary sclerites as well as the posterior notal wing process. Changes in these domains are consistent with the established fate map of the wing disc. We show that outstretched wing posture phenotypes arise from the loss of a region of Unpaired expression in the proximal wing fold and demonstrate that this results in a decrease in JAK/STAT pathway activity. Finally we show that reduction of JAK/STAT pathway activity within the proximal wing fold is sufficient to phenocopy the outstretched phenotype. Taken together, we suggest that localised Unpaired expression and hence JAK/STAT pathway activity, is required for the morphogenesis of the adult wing hinge, providing new insights into the link between signal transduction pathways, patterning and development.