The role of the formin gene fhod-1 in c. elegans embryonic morphogenesis

Abstract

Elongation of the C. elegans embryo from a ball of cells into the long, thin wom1 shape is a tightly controlled and rapid process (2 hr at 20°C). In order for elongation to occur, a highly organized cytoskeleton composed of actin microfilaments, microtubules and intermediate filaments must be fom1ed throughout the epidermis of the embryo, and this must be properly attached to the critical cell-cell adherens junctions. This architecture allows the lateral epidermal cells on the left and right side on the embryo to undergo a tightly regulated and redundantly controlled smooth muscle-like actin/myosin based contraction. This contraction constricts the lateral epidem1al cells in the dorsal/ventral axis and this is transmitted throughout the epidermis, causing a four-fold lengthening in the anterior/posterior axis. Loss the cytoskeletal components or activators of contraction causes the embryo to arrest without elongation, a phenotype incompatible with survival. Loss of inhibitors of contraction or of cell adhesion components, conversely, causes the embryo to rupture during elongation, leading to death. Much of the previous work on elongation has focused on identifying regulators that control the actin-myosin contraction or components of cell adhesion/adherens junction complex. This thesis focuses on FHOD-1, the first protein described whose loss causes defects in the formation of the highly organized circumferential actin microfilament cytoskeleton, which is required for elongation. The worm genefhod-1 encodes a formin homology protein, which in other systems acts to nucleate microfilaments. Overall, l show that an isoform of FHOD-1 interacts genetically with Rho kinase/myosin phosphatase pathway (encoded by the C. elegans genes let-502and mel-11, respectively), is expressed in the lateral epidermal cells where contraction occurs and that loss offhod-1 results in impenetrant elongation arrest and disorganized actin filaments in the lateral epidermis.