Beyond the Identification of Transcribed Sequences: Functional and Expression Analysis

9th Annual Workshop, October 28-31, 1999

Co-sponsored by the U.S. Department of Energy


KOHARA

Post-genomics strategies in C. elegans toward understanding of the molecular mechanisms of development

Yuji Kohara

Genome Biology Lab, National Institute of Genetics, Mishima, Japan

We think the main targets in the post genomics era are as follows: (1) to integrate the information on the expression and the function of all genes of the genome in the context of development, (2) to extract the rules that govern the molecular mechanisms of development that are carried out by a finite number of genes, (3) ultimately to reconstruct the developmental process in the computer.

We have identified about 10,000 cDNA species (more than a half of all genes) of the nematode C.elegans through our EST project.  About 4,000 cDNA species mostly from chromosome 3 (autosome) and X (sex chromosome) have been analyzed by using of whole mount in situ hybridization for mRNA distribution throughout the life of worm.  The mRNA patterns were classified into several categories; maternal expression, zygotic expression, expression in a specific cell lineage but at different time, expression in specific cell(s) and so on.  Based on the information, we are performing clustering analyses and finer analysis on subsets of the genes to elucidate the network of gene regulation.  As a trial, focusing on the early embyrogenesis, we selected a subset of 100 genes on the criteria that the mRNA was expressed maternally and disappeared quickly before gastrulation, which seemed to play important roles in this period.  For these genes, we are analyzing (i) the phenotypes caused by the systematic RNAi (dsRNA mediated interference) experiments, (ii) the protein distribution through the systematic raising of antibodies, and (iii) interacting genes by the yeast two hybrid technology. To integrate and analyse the information, first we have established a WWW-based database NEXTDB, and recently we are constructing a computer graphics based 4-dimensional (3D + time course) database that covers the early embryogenesis.


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