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Rab11 negatively regulates wingless preventing JNK-mediated apoptosis in Drosophila epithelium during embryonic dorsal closure

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Abstract

Rab11, a small Ras like GTPase marking the recycling endosomes, plays instrumental roles in Drosophila embryonic epithelial morphogenesis where an array of reports testify its importance in the maintenance of cyto-architectural as well as functional attributes of the concerned cells. Proper Rab11 functions ensure a precise regulation of developmentally active cell signaling pathways which in turn promote the expression of morphogens and other physico-chemical cues which finally forge an embryo out of a single layer of cells. Earlier reports have established that Rab11 functions are vital for fly embryonic development where amorphic mutants such as EP3017 homozygotes show a fair degree of epithelial defects along with incomplete dorsal closure. Here, we present a detailed account of the effects of Rab11 loss of function in the dorso-lateral epithelium which resulted in severe dorsal closure defects along with an elevated JNK-Dpp expression. We further observed that the dorso-lateral epithelial cells undergo epithelial to mesenchymal transition as well as apoptosis in Rab11 mutants with elevated expression levels of MMP1 and Caspase-3, where Caspase-3 contributes to the Rab11 knockout phenotype contrary to the knockdown mutants or hypomorphs. Interestingly, the elevated expressions of the core JNK-Dpp signaling could be rescued with a simultaneous knockdown of wingless in the Rab11 knockout mutants suggesting a genetic interaction of Rab11 with the Wingless pathway during dorsal closure, an ideal model of epithelial wound healing.

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Acknowledgements

We thank the fly community for generously providing fly stocks. Special acknowledgements to Professor B.J. Rao for providing the TRE-JNK/CyO fly stock and Dr. A. Satoh for providing the anti-Myo V antibody. We thank Dr. Satish Sasikumar and Dr. Tanmay Bhuin for their pioneering studies on the functions of Rab11 on Drosophila embryonic epithelial morphogenesis. Special thanks to Mr. Rohit Kunar for his critical suggestions during the preparation of the manuscript. We duly acknowledge the equipment support of DST-FIST, UGC-CAS, IoE to Department of Zoology and the National facility for Laser Scanning Confocal Microscopy, and Department of Zoology, Banaras Hindu University.

Funding

We sincerely thank the University Grants Commission, New Delhi, and Indian Council of Medical Research, New Delhi, for providing the fellowships to NN.

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  1. Cytogenetics Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, 221005, India

    Nabarun Nandy & Jagat Kumar Roy

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  1. Nabarun Nandy
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Contributions

Conceptualization: NN and JKR. Methodology: NN. Investigation: NN. Visualization: NN. Project administration: JKR. Supervision: JKR. Writing–original draft: NN. Writing–review and editing: NN and JKR.

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Correspondence to Jagat Kumar Roy.

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Summary

Functional loss of Rab11 affects dorsal closure in Drosophila embryos by an ectopic induction of Caspase-3 expression through a genetic interaction with wingless.

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Nandy, N., Roy, J.K. Rab11 negatively regulates wingless preventing JNK-mediated apoptosis in Drosophila epithelium during embryonic dorsal closure. Cell Tissue Res 391, 485–504 (2023). https://doi.org/10.1007/s00441-023-03740-2

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