Wdr62 and Patronin cooperate to organize distinct acentrosomal microtubule networks during Drosophila oogenesis

Abstract

Acentrosomal microtubule (MT) organization is essential in many differentiated cells, yet the mechanisms that generate and maintain these networks remain poorly understood. Here, we identify Wdr62 as a conserved regulator of acentrosomal MT organization during Drosophila oogenesis. Wdr62 localizes to cortical non-centrosomal microtubule-organizing centers (ncMTOCs) and is required for proper localization of the conserved components Shot and Patronin. Loss of Wdr62 disrupts MT organization and oocyte polarity and reduces MT growth events during mid-oogenesis. Genetic analyses further reveal that Wdr62 functionally cooperates with Patronin and the MT-severing enzyme Katanin 80 to organize the acentrosomal MT network. Our data support a model in which Wdr62 promotes stabilization of MT minus ends through Patronin while Katanin-mediated severing generates new MT seeds that amplify the MT network. Moreover, Wdr62 and Patronin function together during assembly of the acentrosomal meiotic spindle, and their loss compromises fertility. Given that WDR62 mutations are associated with human disease in cell types that rely on acentrosomal MT organization, such as neurons, these findings provide insight into how disruption of WDR62-dependent MT organization may contribute to disease beyond female infertility.