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. 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. and Ueno, N. (1999). Development, in press. 2. Savage, S., Padgett, R., and Baird, S. (1994) WBG 13(2): 38 3. Shetgiri, P., Krishna, S., Savage, C., and Padgett, R. W. (1997) International Worm Meeting Abstract 539 4. Vellai, T. and Fodor, A. (1997) WBG 14(5): 59. 5. de Bono, M. and Bargmann, C. (1997) International Worm Meeting Abstract 121