Mutations in genes encoding a signal transduction pathway activated by a ligand in the TGF- faimly, DBL-1 can profoundly affect body size in C. elegans. Loss of function mutations in genes in the pathway causes a Sma phenotype characterized by a marked reduction in body size whereas constitutive activation of the pathway increases 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 efffects in part at least by affecting endoreduplicaton of hypodermal nuclei, and in part by regulating expression of components of the cuticle. Two targets of the pathway have been identified,
lon-1which encodes a PR-related protein and
lon-3 which encodes a cuticle collagen1, 2, 3, 4. Mutations in
lon-1 affect both endoreduplication and body length, whereas mutations in
lon-3 affect length without affecting endoreduplication. In a screen for new mutations causing a Lon phenope we have isolated 2 alleles,
sp10 and
sp11, of a locus on X, lying between
unc-9 and
lin-15. The mutations are all recessive and 100% penetrant; homozygous mutants are approximately 23 % longer than wild type but display no other obvious defects. Morphometric analysis indicates that the phenotype caused by these mutations is very similar to that caused by overexpression of DBL-1. We have identified a cosmid that rescues the mutant phenotype. The screen also identified a single allele,
sp9, of a locus between
unc-3 and
lin-15 on X. This mutation causes an incompletely penetrant Lon phenotype; homozygous mutants are also slightly Egl. 1. Morita K, Flemming AJ, Sugihara Y, Mochii M, Suzuki Y, Yoshida S, Wood WB, Kohara Y, Leroi AM, Ueno N, EMBO 21: 1063-1073 (2002); 2. Maduzia LL, Gumienny TL, Zimmerman CM, Wang H, Shetgiri P, Krishna S, Roberts AF, Padgett RW, Developmental Biology 246: 418-428 (2002); 3. Nystrom J, Shen ZZ, Aili M, Flemming AJ, Leroi A, Tuck S, Genetics 161: 83-97 (2002); 4. Suzuki Y, Morris GA, Han M, Wood WB, Genetics 162:1631-1639 (2002).