Mutants carrying two sma mutations are super small in the nematode C. elegans.

Body size determination is critical for multicellular organisms; however, the mechanisms remain largely unknown. Mutations that alter body size were studied to solve the mechanisms, for example, in mouse, fruit fly and the nematode Caenorhabditis elegans. In C. elegans, a large mutant and several small body size (sma) mutants are known. Of the latter, sma-2, sma-3, sma-4, sma-6, dbl-1 and daf-4 have a mutation in the components of the DBL-1/TGFbeta signal pathway, and sma-5 in a MAP kinase homologue. We have constructed double mutants carrying two of such small body size mutations, sma-5 and sma-4 or sma-2. They are much smaller than either of the parental single mutants, indicating that the sma-5 gene functions independently of the DBL-1/TGFbeta pathway. We show that their body volumes are as small as 1/10 of that of the wild-type, and that the sizes of major organs are much reduced, by the methods previously developed by us. But the numbers of cells are not changed, suggesting that the cells are very small. These results highlight surprising flexibility of body size and cell size in a multicellular organism, which will give a novel insight into the mechanisms of body size control.