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Dorsal closure during Drosophila embryogenesis provides a robust genetic platform to study the basic cellular mechanisms that govern epithelial wound healing and morphogenesis. As dorsal closure proceeds, the lateral epithelial tissue (LE) adjacent to the dorsal opening advance contra-laterally, with a simultaneous retraction of the amnioserosa. The process involves a fair degree of coordinated cell shape changes in the dorsal most epithelial (DME) cells as well as a few penultimate rows of lateral epithelial (LE) cells (collectively referred here as Dorsolateral Epithelial (DLE) cells), lining the periphery of the amnioserosa, which in due course of time extend contra-laterally and ultimately fuse over the dorsal hole, giving rise to a dorsal epithelial continuum. The JNK-Dpp signaling in the dorsolateral epidermis, plays an instrumental role in guiding their fate during this process. A large array of genes have been reported to be involved in the regulation of this core signaling pathway, yet the mechanisms by which they do so is hitherto unclear, which forms the objective of our present study. Here we show a probable mechanism via which lgl, a conserved tumour suppressor gene, regulates the JNK-Dpp pathway during dorsal closure and epithelial morphogenesis. A conditional/targeted knock-down of lgl in the dorsolateral epithelium of embryos results in failure of dorsal closure. Interestingly, we also observed a similar phenotype in a Rab11 knockdown condition. Our experiment suggests Rab11 to be interacting with lgl as they seem to synergize in order to regulate the core JNK-Dpp signaling pathway during dorsal closure and also during adult thorax closure process., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Rab11, a member of Rab-GTPase family, and a marker of recycling endosomes has been reported to be involved in the differentiation of various tissues in Drosophila. Here we report a novel role of Rab11 in the differentiation of stellate cells via the non-canonical Notch pathway in Malpighian tubules. During Malpighian tubule development caudal visceral mesodermal cells intercalate into the epithelial tubule of ectodermal origin consisting of principal cells, undergo mesenchymal to epithelial transition and differentiate into star shaped stellate cells in adult Malpighian tubule. Two transcription factors, Teashirt and Cut (antagonistic to each other) are known to be expressed in stellate cells and principal cells, respectively, from early stages of development and serve as markers for these cells. Inhibition of Rab11 function or over-expression of activated Notch in stellate cells resulted in the expression of Cut that leads to down-regulation of Teashirt or vice-versa that leads to hampered differentiation of stellate cells. The stellate cells do not transform to star/bar shaped and remain in mesenchymal state in adult Malpighian tubule. Over-expression of Deltex, which plays important role in non-canonical Notch signaling pathway, shows similar phenotype of stellate cells as seen in individuals with down-regulated Rab11, while down-regulation of Deltex in genetic background of Rab11 RNAi rescues Teashirt expression and shape of stellate cells. Our experiments suggest that an inhibition or reduction of Rab11 function in stellate cells results in the faulty recycling of Notch receptors to plasma membrane as they accumulate in early and late endosomes, leading to Deltex mediated non-canonical Notch activation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The present work elucidates the role of miRNA in cell cycle regulation during brain development in Drosophila. Here we report that lineage specific depletion of dicer-1, a classically acknowledged miRNA biogenesis protein in neuroblasts leads to a reduction in their numbers and size in the third instar larval central brain. These brains also showed lower number of mitotically active cells and when homozygous mitotic clones were generated in an otherwise heterozygous dicer-1 mutant background via MARCM technique, they showed reduced number of progeny cells in individual clones, substantiating the adverse effect of the loss of dicer-1 on the proliferative potential of neuroblasts. bantam miRNA, which has been classically reported to be involved in tissue growth was found to express in neuroblasts and undergo reduced expression in Dicer-1 depleted background in the third instar larval brain. Reduction in the number and proliferative potential of neuroblasts in bantam mutant background implies a pivotal role played by bantam miRNA in maintenance of neuroblast number. Since, in both Dicer-1 and bantam depleted genetic backgrounds, Dacapo, an inhibitor of cyclin E-Cdk complex, was found to have elevated expression, we put forward a molecular mechanism involving bantam-Dacapo-Cyclin E/Cdk complex that regulates the G1-S phase transition of Drosophila neuroblasts., (Copyright © 2017 Elsevier Inc. All rights reserved.)