Worm Breeder's Gazette 15(5): 44 (February 1, 1999)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Mediators and Modulators of dbl-1 Functions in Body Size Control

Yo Suzuki, Gail Morris, Bill Wood

Department of MCD Biology, University of Colorado, Boulder, CO 80309-0347

Size regulation of body components is a poorly understood aspect of animal growth and development. We have previously shown that the activity of the dbl-1 gene, a C. elegans gene encoding a TGF-b ligand, is critical for cell-size and body-size control during post-embryonic development of the worm (1). Identification of additional downstream targets that mediate dbl-1 functions and of upstream regulators that modulate the activity of dbl-1 could provide new insights into the mechanisms of size regulation.

Loss-of-function (lf) mutations in dbl-1 result in a Sma phenotype, whereas the overexpression of dbl-1 results in a Lon phenotype (1). These results suggest that mutations affecting the activity of dbl-1 could be identified by screening for these convenient phenotypes. 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. We plan genetic and molecular characterization of genes defined by these suppressors.

Previous studies on the epistatic relationships between sma genes and lon genes placed lon-2 and lon-3 upstream and lon-1 downstream of the genes encoding the receptors and the Smad proteins of the body size control pathway (2). In similar experiments, we have shown that dbl-1(lf) mutations are epistatic to lon-2 and lon-3 mutations, suggesting that these two lon genes act upstream of dbl-1 as well, and are thus possible modulators of dbl-1 activity. lon-1 and lon-2 are being studied in other laboratories (3, 4, 5). We are attempting to clone lon-3 and have obtained cosmid rescue. Rescuing arrays can cause a Sma phenotype, suggesting the possibility that lon-3, like dbl-1, is a dose-dependent regulator of body size. We hope to elucidate how dbl-1 and lon-3 interact.