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 Rab11RNAi 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.

中文翻译：

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Rab11在果蝇Malpighian小管中通过非规范的Notch途径在星状细胞分化中起关键作用。

据报道，Rab11是Rab-GTPase家族的成员，是回收内体的标志物，与果蝇中各种组织的分化有关。在这里，我们报告Rab11在通过Malpighian小管中的非规范Notch途径分化星状细胞中的新型作用。在Malpighian小管发育期间，尾脏内脏中胚层细胞插入由主要细胞组成的外胚层起源的上皮小管中，经历间质向上皮的转变，并在成年的Malpighian小管中分化为星形星状细胞。从发育的早期开始，已知两种转录因子，即Teashirt和Cut（彼此拮抗）分别在星状细胞和原代细胞中表达，并充当这些细胞的标记。星状细胞中Rab11功能的抑制或活化的Notch的过表达导致Cut的表达，导致Cutle的下调，反之亦然，导致星状细胞的分化受阻。星状细胞不会转化为星形/条状，并在成年的马尔皮基小管中保持间充质状态。在非典型的Notch信号通路中起重要作用的Deltex的过度表达显示出与下调Rab11的个体相似的星状细胞表型，而在Rab11RNAi遗传背景下Deltex的下调可挽救茶衫的表达和形状星状细胞。