The object of this grant is to gain a better understanding of how the actin cytoskeleton functions during early embryonic development and in the establishment of polarity. Numerous studies have demonstrated that the actin cytoskeleton plays a prominent, but poorly understood, role during the early embryogenesis of multicellular organisms and an important role in the establishment of embryonic polarity. The early C. elegans embryo provides an excellent system for investigating these topics since: (1) its development is well-characterized and displays striking actin-dependent asymmetries; and (2) it is amenable to study by forward and reverse genetics, lineage analysis, cell biology, molecular biology, and biochemistry.
The investigator's laboratory has identified by biochemical chromatography 17 C. elegans actin binding proteins (CABPs) from oocytes (Aroian et al., 1997). Since actin binding proteins (ABPs) are important mediators of actin function, studies of CABPs are apt to provide significant new insights into the functions of the actin cytoskeleton during early embryogenesis. One CABP, CABP11, was cloned by screening an expression library and shows limited homology to a known ABP, Coronin. CABP11, is asymmetrically localized, and, based on data using RNA-mediated interference (RNAi), plays a role in establishing embryonic polarity and blastomere identity. It is hypothesized that CABP11 is involved in organizing the early embryonic cortex and plasma membrane. Using mass spectroscopy (MS), the sequences of two other CABPs have been recently identified. One of these is a member of the myosin II family and is asymmetrically localized; the other is a heat shock protein.
Given what is known about the important role of the actin cytoskeleton in early embryogenesis, the investigator's research aims to help fill in a significant gap in knowledge. Studies on early embryogenesis are apt to lead to a better understanding of cell identity, cell polarity, and cell division, all of which play prominent roles during this time of development. Information on the regulation of the actin cytoskeleton is potentially relevant for understanding signal transduction, cell-cell signaling, cell motility, control of cell shape and integrity, and wound healing.
