Understanding the role of dPak3 in mediating guidance of border cells during Drosophila oogenesis

Felix, Martina (2021) Understanding the role of dPak3 in mediating guidance of border cells during Drosophila oogenesis. PhD thesis, Indian Institute of Science Education and Research Kolkata.

Text (PhD thesis of Martina Felix (17RS039)) 17RS039.pdf - Submitted Version Restricted to Repository staff only Download (5MB)

Abstract

Collective cell migration plays a crucial role during several physiological processes such as gastrulation, tissue morphogenesis, wound healing, and unfortunately tumor cell metastasis. Cells migrating in a cohort, retain cellular adhesion and some degree of apical-basal polarity quite distinct from single-cell movement. Though much is known about group cell movement, how polarity is regulated in such a multicellular context is far from clear. Here we employ border cell migration during Drosophila oogenesis as a model to study polarity during multicellular movement. Drosophila ovary consists of strings of egg chambers called ovariole. Each egg chamber consists of sixteen germline cells (fifteen nurse cells and one oocyte) surrounded by a layer of epithelial follicle cells. At stage 8, six-eight anterior follicle cells specified by the specialized polar cells, round up, detach, and migrate to reach the oocyte boundary. These cells are known as the border cells. Border cell migration aids in sperm entry during fertilization. Pak3 a p21 serine-threonine protein kinase functions downstream of guidance receptor signaling to modulate the polarized movement of border cells. Pak3 deficit border cells undergo incomplete migration. Time-lapse imaging of Pak3 deficient border cells indicates that Pak3 modulates protrusive behavior of the border cells during migration regulating the length, stability, and directionality of the actin-rich protrusions. Pak3 functions downstream of guidance receptor signaling to regulate F-actin distribution in the migrating border cells. It interacts with scribble, a lateral polarity determinant. Down regulation of Pak3 in the migrating cluster affects the level of pJun. Pak3 deprived cluster exhibits mis localization of several apical-basal polarity regulators. Over-expression of Jra suggests that Pak3 functions through JNK signaling to regulate the distribution of apical-basal polarity proteins in the migrating border cells. Rac1 deficient cluster also shows mis localization of apical-basal polarity proteins suggesting that guidance receptor signaling functions through Rac GTPase and Pak3 to regulate the overall polarity of the cluster and mediate efficient collective movement of the border cells to the oocyte boundary. Finally, we show that Pak3 and aPKC function antagonistically to regulate the distribution of apical-basal polarity proteins during border cell migration. Altogether, my results give a nice insight into how polarity is regulated in a migrating cohort with long term implications in understanding both normal development and diseased conditions

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