Cell Topology Change by the Physical Engagement of Neighboring Cytoskeletal Networks

Cell topology changes are often associated with neighboring zones of distinct actin cytoskeletal networks and regulators, such as lamellipodium and lamella in migratory cells, branched and unbranched actin networks at cell-cell contacts, and concentric rings of Rho family GTPases during wound healing. Neighboring networks can cooperate, antagonize and interconvert through both physical and chemical mechanisms, but how these interactions modulate overall cell shape remains unclear. My research examined the metaphase furrowing mechanism of the syncytial Drosophila embryo. Prior to furrowing, an actin cap, consisting of Sponge (Spg, a Rac GEF), SCAR/WAVE, and Arp2/3, forms on top of each nucleus. Each cap is encircled by actomyosin borders, enriched with Rho signaling effectors (Rok, myosin, Dia, anillin, and anillin-recruited septins). Each network has only been studied individually. To understand their dynamics together, I first tracked them in the live embryos. Strikingly, the cap networks expand, meet the segregated actomyosin borders, and then bend downward to coat the nascent furrows. Concomitantly, the myosin borders become restricted to the furrow base. These observations let us hypothesize both networks antagonize each other through physical interaction. Indeed, increasing or decreasing myosin contractility resulted in restricted or enhanced actin cap growth, respectively, indicating myosin borders restrict and organize the expanding caps. Inversely, the cap growth physically pushed the actomyosin borders, displacing mesoscale structures into the furrows. Their physical contact not only refines the organization of each network but also induces buckling of the embryo cortex for metaphase furrowing. Buckling of the actin caps appears to be sufficient for forming the compartments, but normally these domains also swell through the contraction of the neighboring actomyosin borders. Overall, my thesis outlines mechanisms to explain how the physical interplay between mutually exclusive actin domains patterns the cortex and drives cell topology change. These mechanisms could be broadly applicable to systems involving the formation of a small compartment from a bigger cell.

Department dc:contributor.department

Cell and Systems Biology

Year dc:date.issued

2018

Author dc:creator

• Zhang, Yixie

Advisor dc:contributor.advisor

• Harris, Tony J.C.

• Actin
• Drosophila
• embryo cleavage
• Myosin
• Syncytium

Handle dc:identifier.uri

http://hdl.handle.net/1807/92112

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/92112