Molecular and Genetic Analysis of Germline Development in C. Elegans

Syracuse University, Syracuse NY

Investigators

Abstract

0077172 Maine The proposed studies investigate the regulation of cell fate during animal development. Experiments focus on how cell proliferation is regulated in germline tissue of the model organism, C. elegans. Germline proliferation in C. elegans is stimulated by a signal from cells in the somatic gonad. Germ cells that receive the signal will divide, whereas those that do not receive the signal will stop dividing and instead differentiate as sperm or eggs. This signaling occurs via a "Notch-type" biochemical pathway. Notch-type signaling pathways regulate development in diverse animal species; in mammals, they are implicated in certain cancers and other diseases. Many questions remain about the regulation of germline proliferation in C. elegans and how Notch-type signaling provokes a specific cellular response. For example, little is known about the targets of pathway activity or how pathway activity is regulated. Possible targets in the C. elegans germ line include genes that promote formation of gametes, such as gld-1 and gld-2. Notch-type signaling could promote proliferation by turning off gld-1 and gld-2 gene expression. To better understand how germline development is regulated, Dr. Maine and colleagues have identified and studied genes that interact genetically with a known component of the signaling pathway, glp-1. Here, Dr. Maine proposes to extend the analysis of several "ego" (enhancer of glp-1) genes. Previous studies from the Maine laboratory indicate that ego-1 gene activity is critical for both germline development and a poorly understood process called RNA silencing. RNA silencing is a means of gene regulation that has been observed in plants, animals, and fungi. It is thought to be a defense against viral infection, but the P.I. has data to suggest that it may also be an important regulatory mechanism during development. Consequently, she proposes to investigate potential target genes that might be regulated by RNA silencing during germline development, including gld-1 and gld-2. Several complementary studies will investigate (1) the expression of EGO-1 protein during germline development, (2) whether EGO-1 is essential for phenomena related to RNA silencing, (3) potential genetic interactions between ego-1 and other genes involved in RNA silencing, and (4) the role of EGO-1 in meiotic chromosomal pairing. Related studies will investigate other ego genes. They will be tested to determine if they function in RNA silencing; if so, then molecular studies will be initiated. Molecular studies of ego-3 will determine the nature of its gene product and how it functions to promote germline proliferation. Analysis of ego-3 will receive reduced effort if it does not function in RNA silencing while other Ego genes do so function