A Cdc42-regulated actin cytoskeleton mediates Drosophila oocyte polarization

Abstract

Polarity of the Drosophila oocyte is essential for correct development of the egg and future embryo. The Par proteins Par-6, aPKC and Bazooka are needed to maintain oocyte polarity and localize to specific domains early in oocyte development. To date, no upstream regulator or mechanism for localization of the Par proteins in the oocyte has been identified. We have analyzed the role of the small GTPase Cdc42 in oocyte polarity. We show that Cdc42 is required to maintain oocyte fate, which it achieves by mediating localization of Par proteins at distinct sites within this cell. We establish that Cdc42 localization itself is polarized to the anterolateral cortex of the oocyte and that Cdc42 is needed for maintenance of oocyte polarity throughout oogenesis. Our data show that Cdc42 ensures the integrity of the oocyte actin network and that disruption of this network with Latrunculin A phenocopies loss of Cdc42 or Par protein function in early stages of oogenesis. Finally, we show that Cdc42 and Par proteins, as well as Cdc42/Par and Arp3, interact in the context of oocyte polarity, and that loss of Par proteins reciprocally affects Cdc42 localization and the actin network. These results reveal a mutual dependence between Par proteins and Cdc42 for their localization, regulation of the actin cytoskeleton and, consequently, for the establishment of oocyte polarity. This most likely allows for the robustness in symmetry breaking in the cell.

Cytoskeletal Symmetry Breaking and Chirality: From Reconstituted Systems to Animal Development

“…The cortical actin network is however directly responsible for localization of the polarity factor Par1 [275] and together with polarized localization of the polarity regulator Cdc42 involved in oocyte polarization through positive feedback onto the Par3/Par6/aPKC polarity complex [276].…”

Apical transport of Crumbs maintains epithelial cell polarity

“…However, the actin cytoskeleton is not strictly required for polarization of the worm zygote, which can also be triggered by a microtubule-based mechanism (Motegi et al, 2011;Zonies et al, 2010). In Drosophila and mammalian oocytes, the actin cytoskeleton is polarized and plays an important role with Cdc42 in breaking symmetry (Leblanc et al, 2011;Leibfried et al, 2013;Ma et al, 2006;Wang et al, 2013;Yi et al, 2013;Yi et al, 2011;Zhang et al, 2008). In epithelial cells, which of these two mechanisms, oligomeric clustering of determinants versus cytoskeletal transport of determinants, is responsible for directing polarity remains a fundamental unsolved problem.…”

Drosophila glob1 is required for the maintenance of cytoskeletal integrity during oogenesis

“…Here, it is worth noting that several actin‐associated proteins have been reported to be vital for the maintenance of the integrity of F‐actin‐based specialized structures during oogenesis (Hudson and Cooley, ). Mutations in several genes such as arpc1, arp3, dpak, kugel, src64, cdc42, chickadee , etc., have been found to alter the dynamics of F‐actin, which in turn leads to various abnormalities during oogenesis (Cooley et al, ; Hudson and Cooley, ; Hudson and Cooley, ; Djagaeva et al, ; Conder et al, ; Sarkar and Lakhotia, ; Bahri et al, ; Leibfried et al, ). Interestingly, the pattern of abnormalities perceived in distribution and assembly of F‐actin due to reduced expression of glob1 were somewhat similar to those reported in the mutants of the above‐mentioned genes.…”