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Identifying the upstream signals and the downstream effects of the WAVE/SCAR complex during embryonic morphogenesis

by
Yelena Bernadskaya
M.S., New York University - 2006


Thesis Advisor: Martha Soto, Ph.D.
Graduate Program in Cellular & Developmental Biology

Life Science Building Auditorium
145 Bevier Road
Piscataway

Tuesday, May 29, 2012
11:00 a.m.


Abstract

Understanding how normal cell migration is genetically and molecularly controlled is of paramount importance to understanding aberrant cell migrations that occur during metastatic cancers. We use the C. elegans model to study the migration of a sheet of epidermal cells during the process of morphogenesis. At this stage, the epidermal cells must migrate from the dorsal side of the embryo to the ventral side to complete ventral enclosure. We have found that the main pathway required for this migration is the CED-10/Rac-WAVE/SCAR-Arp2/3 pathway that regulates enrichment of actin at the leading edge of migrating cells. Using genetic, molecular, and biochemical techniques we investigated the role of Arp2/3 during morphogenesis of the two epithelial tissues, the epidermis and the intestine. In the work described here we show that (a) the WAVE/SCAR-Arp2/3 pathway is required during epidermal cell migration to induce the formation of cell protrusions that are needed for the migration of the epidermis to take place, (b) that three axonal guidance cues, UNC-40/Netrin receptor, SAX-3/Robo, and VAB-1 receptor act as upstream regulators of the WAVE/SCAR pathway and are required to correctly localize CED-10/Rac and WAVE/SCAR, thereby correctly polarizing actin in the migrating epidermis, and (c) that Arp2/3 dependent branched actin has a positive role in establishing polarity of epithelial tissues and maintaining the integrity of cell junctions and their association with their target membranes. These studies suggest that the WAVE/SCAR pathway can integrate multiple cues to tightly regulate actin polymerization and orientation during cell migration and has an intrinsic function in establishing and maintaining polarity of other epithelial tissues.


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