Filamin is required for ring canal assembly and actin organization during Drosophila oogenesis

The remodeling of the actin cytoskeleton is essential for cell migration, c ell division, and cell morphogenesis. Actin-binding proteins play a pivotal role in reorganizing the actin cytoskeleton in response to signals exchang ed between cells. In consequence, actin-binding proteins are increasingly a focus of investigations into effecters of cell signaling and the coordinat ion of cellular behaviors within developmental processes. One of the first actin-binding proteins identified was filamin, or actin-binding protein 280 (ABP280). Filamin is required for cell migration (Cunningham et al,, 1992) , and mutations in human alpha-filamin (FLN1; Fox et al., 1998) are respons ible for impaired migration of cerebral neurons and give rise to periventri cular heterotopia, a disorder that leads to epilepsy and vascular disorders , as well as embryonic lethality. We report the identification and characte rization of a mutation in Drosophila filamin, the homologue of human alpha- filamin. During oogenesis, filamin is concentrated in the ring canal struct ures that fortify arrested cleavage furrows and establish cytoplasmic bridg es between cells of the germline. The major structural features common to o ther filamins are conserved in Drosophila filamin. Mutations in Drosophila filamin disrupt actin filament organization and compromise membrane integri ty during oocyte development, resulting in female sterility, The genetic an d molecular characterization of Drosophila filamin provides the first genet ic model system for the analysis of filamin function and regulation during development.