Body size in C. elegans is regulated by a TGF-beta family ligand, DBL-1. Loss-of-function mutations in
dbl-1 cause a Sma phenotype characterized by a marked reduction in body size whereas worms overexpressing
dbl-1 have increased body length (Lon). Worms displaying the Sma or Lon phenotypes appear to have the same numbers of cells as wild type suggesting that the pathway affects body size by affecting cell size rather than cell number. The pathway may excert its effects in part by affecting endoreduplicaton of hypodermal nuclei, and in part by regulating expression of components of the cuticle. One target of the pathway is
lon-3, a cuticle collagen, which is negatively regulated at a posttranscriptional level(1, 2). Loss of function mutations in
lon-3 causes a Lon phenotype similar to that caused by overexpression of DBL-1; elevated levels on the other hand cause a Dpy phenotype. In order to identify new genes involved in body length regulation we are screening for mutations that suppress the Dpy phenotype caused by elevated levels of
lon-3. From a screen of 98,000 haploid genomes we have isolated 16 mutations that suppress the Dpy phenotype caused by svIs32[
lon-3(+)]. One is an allele of
lon-2 X, a known negative regulator of TGF-b signalling. One mutation causes a thin phenotype without affecting body length. 4 mutations, mapping to linkage groups I, II, III, and IV respectively, cause a Lon phenotype. The others, while acting as efficient suppressors, do not appear to cause a marked increase in body length in an otherwise wild-type background. We are presently mapping the mutations further and screening for more suppressors. (1) Nystrom J., Z. Z. Shen, M. Aili, A. J. Flemming, A. Leroi, and S. Tuck. Genetics 161: 83-97 (2002); (2) Suzuki Y., G. A. Morris, M. Han, and W. B. Wood. Genetics 162:1631-1639 (2002).