Canonical Wnt signalling regulates epithelial patterning by modulating levels of laminins in zebrafish appendages.

The patterning and morphogenesis of body appendages - such as limbs and fins - is orchestrated by the activities of several developmental pathways. Wnt signalling is essential for the induction of limbs. However, it is unclear whether a canonical Wnt signalling gradient exists and regulates the patterning of epithelium in vertebrate appendages. Using an evolutionarily old appendage - the median fin in zebrafish - as a model, we show that the fin epithelium exhibits graded changes in cellular morphology along the proximo-distal axis. This epithelial pattern is strictly correlated with the gradient of canonical Wnt signalling activity. By combining genetic analyses with cellular imaging, we show that canonical Wnt signalling regulates epithelial cell morphology by modulating the levels of laminins, which are extracellular matrix components. We have unravelled a hitherto unknown mechanism involved in epithelial patterning, which is also conserved in the pectoral fins - evolutionarily recent appendages that are homologous to tetrapod limbs.

Myosin Vb mediated plasma membrane homeostasis regulates peridermal cell size and maintains tissue homeostasis in the zebrafish epidermis.

The epidermis is a stratified epithelium, which forms a barrier to maintain the internal milieu in metazoans. Being the outermost tissue, growth of the epidermis has to be strictly coordinated with the growth of the embryo. The key parameters that determine tissue growth are cell number and cell size. So far, it has remained unclear how the size of epidermal cells is maintained and whether it contributes towards epidermal homeostasis. We have used genetic analysis in combination with cellular imaging to show that zebrafish goosepimples/myosin Vb regulates plasma membrane homeostasis and is involved in maintenance of cell size in the periderm, the outermost epidermal layer. The decrease in peridermal cell size in Myosin Vb deficient embryos is compensated by an increase in cell number whereas decrease in cell number results in the expansion of peridermal cells, which requires myosin Vb (myoVb) function. Inhibition of cell proliferation as well as cell size expansion results in increased lethality in larval stages suggesting that this two-way compensatory mechanism is essential for growing larvae. Our analyses unravel the importance of Myosin Vb dependent cell size regulation in epidermal homeostasis and demonstrate that the epidermis has the ability to maintain a dynamic balance between cell size and cell number.

Association of promoter region polymorphisms of CD209 gene with clinical outcomes of dengue virus infection in Western India.

Dendritic cell specific intercellular adhesion molecule 3 grabbing non-integrin, coded by the CD209 gene, acts as an entry receptor for dengue virus. Polymorphisms in the promoter region of CD209 gene (rs735239, rs4804803, rs2287886) were investigated in 112 hospitalized cases of dengue (DEN) and 104 healthy controls to find out whether they are associated with dengue in a Western Indian population. Results revealed a significantly higher frequency of 'G' allele and 'G/G' genotype of rs2287886 and A-A-G haplotype of CD209 gene in DEN compared to healthy controls [For 'G/G' genotype, P=0.0072, Odds ratio (OR) 2.43; For A-A-G haplotype, P=0.0033, OR 2]. The frequency of A/A genotype of rs735239 was higher in DEN cases with thrombocytopenia compared to cases without thrombocytopenia (P=0.026). The results suggest that rs2287886 G/G genotype of CD209 gene is associated with development of dengue requiring hospitalization while A/A genotype of rs735239 is associated with thrombocytopenia in dengue cases.