Size regulation of body components is a poorly understood aspect of animal growth and development. We have previously shown that the
dbl-1 gene, a C. elegans gene encoding a TGF- b ligand, is a dose-dependent positive regulator of cell size and body size increase during post-embryonic development of the worm (1). Identification of additional components that act upstream and downstream of
dbl-1 could provide new insights into the mechanisms of size regulation. Studies of the epistatic relationships between known lon genes and components of the
dbl-1 signal transduction pathway have placed
lon-2 and
lon-3 upstream of
dbl-1 , and
lon-1 downstream of the Smad genes of the pathway (2, 3). More careful analysis has shown, however, that
dbl-1 lon-3 double mutants are small but slightly longer than
dbl-1 single mutants, leaving open the possibility that
lon-3 acts independently of the
dbl-1 pathway. We are in the process of cloning
lon-3 to allow further analysis of its function. To identify potential targets of the body size control pathway, we are carrying out screens for suppressors of the Sma and Lon phenotypes caused by
dbl-1(lf) mutations and
dbl-1 overexpression, respectively. In a screen of 14,000 haploid genomes for suppressors of the Sma phenotype, we have isolated a number of candidate suppressors. Some isolates exhibit phenotypes similar to the Lon-1 phenotype, and others exhibit phenotypes that resemble the semi-Sma phenotypes of
dbl-1 lon-3 double mutants or
dbl-1 heterozygotes. We plan genetic and molecular characterization of genes defined by these suppressors. 1. Suzuki, Y., Yandell, M. D., Roy, P. J., Krishna, S., Savage-Dunn, C., Ross, R. M., Padgett, R. W. and Wood, W. B. (1999). Development 126: 241-250. Similar results have been obtained by Morita, K., Chow, K. L., and Ueno, N. (1999). Development 126: 1337-1347. 2. Savage, S., Padgett, R., and Baird, S. (1994) WBG 13(2): 38 3. Suzuki, Y., Morris, G., and Wood, B. (1999) WBG 15(5): 44