Department of Biology
Massachusetts Institute of Technology
Howard Hughes Medical Institute
McGovern Institute for Brain Research


Research: Introduction

How do genes control animal development and behavior? To answer this question, we isolate developmental and behavioral mutants of the nematode Caenorhabditis elegans and use genetic, molecular, cell biological, pharmacological, electrophysiological and biochemical techniques to characterize these mutants and the genes defined by them. Because the complete cellular anatomy (including the complete wiring of the 302-cell nervous system) and the complete cell lineage of C. elegans are known, mutant animals can be studied at the level of single cells and even single synapses. Because the complete DNA sequence of the C. elegans genome is available, genes defined by mutations can be rapidly cloned and analyzed. In addition, genes and complete gene families defined by sequences similar to those of known genes (e.g., from C. elegans or from other organisms, including humans) can be easily identified and inactivated by isolating deletion mutations and by using the method of RNA-mediated interference (RNAi). Many of our current interests derive from our earlier studies of the control of C. elegans egg laying, which led us to isolate mutants defective in egg laying and then analyze the roles of the genes defined by these mutants in the development and functioning of the egg-laying system and elsewhere in the animal. We have studied many genes that play specific roles in C. elegans development and behavior, including defining members of the POU and LIM transcription factor families and of the RGS signal transduction protein family. These protein families have since been found to play major roles in a variety of biological processes in many organisms. We discovered heterochronic genes (which control developmental timing), defined the core caspase-mediated pathway for programmed cell death (apoptosis) and helped elucidate the Ras pathway for signal transduction. Our work has defined biological mechanisms and pathways that have subsequently been found to be shared among organisms as diverse as nematodes and humans and that have been implicated in a variety of human diseases.

The Horvitz Lab