INVESTIGATING THE ROLE OF ACTIN CAPPING PROTEIN IN TISSUE MORPHOGENESIS AND FUNCTION USING C. ELEGANS AS A MODEL SYSTEM

Abstract

In this thesis, we have explored the role of CAP-1, an actin capping protein during C. elegans embryogenesis and tissue function primarily in the germline. CAP-1 is associated with actin and actomyosin structures across multiple tissues in C. elegans. Embryos lacking cap-1 exhibit ~60% lethality, while failing to develop beyond late embryogenesis stages. We observed defects in actin network organisation and formation of large PLST-1 puncta in embryos lacking cap-1, providing strong evidence for the role of CAP-1 in regulation of actin architecture during embryogenesis. In the germline, loss of cap-1 leads to disruption of the tissue architecture accompanied by constricted and meandering rachis and multinucleated germ cells. In addition to effects on the actin structure, we observed a 2-fold increase in the levels of actin and myosin in the germline, along with a 1.3fold increase in ARX-2 levels, indicating changes in the germline actin network architecture by affecting degree of branching. Increase in myosin II levels suggests an increase in contractility in the germline in the absence of CAP-1. Double knockdown of let-502 (Rho kinase) and cap-1 reverses the germline morphologic defects arising from cap-1 RNAi resulting in a wider rachis, further strengthening the evidence for an increase in actomyosin contractility in cap-1 loss. Taken together, we demonstrate that CAP-1 plays an important role by regulating actin and actomyosin structures in tissue morphogenesis and tissue function.