How to make the nematode C. elegans larger? We pay attention to the transforming growth factor- b (TGF- b ) pathway. TGF- b superfamily ligands have major regulatory effects on growth and differentiation in vertebrates. In C. elegans ,
daf-1 and
daf-4 encode serine/threonine kinase receptors related to TGF- b receptors.
daf-4 mutant animals reveal multiple roles for TGF- b -like signalling and they were reported to be smaller than the wild type. Genes
sma-2,
sma-3 and
sma-4 encode Smad family transcription factors acting in a
daf-4 signalling pathway, and their mutants were also reported to be smaller. Considering these results, we expect that wild type genes for
sma-2,
sma-3,
sma-4 and
daf-4 may have an ability to induce a larger body size phenotype. First we measured the body length and maximum diameter of wild type and those mutant animals and confirmed that they are smaller. We also estimated their body volume in an approximation. We injected each of the wild-type genes
sma-3 and
sma-4 at varied concentrations, and
daf-4 to the corresponding mutants. Some of the transgenic lines with
sma-4 or
sma-3 wild-type gene are nearly completely rescued with respect to the body size (length, maximum diameter and estimated volume). We also injected the
sma-4 wild-type gene into the wild-type animal, and obtained a transgenic line longer than the wild type. The effect of
sma-3 or
sma-4 transgenes on the body size varied. The body size of the transgenic lines partly depends on the concentration of the gene in the injected solutions, and also varied from line to line. For a similar purpose, we are interested in the
sma-5 gene.
sma-5 was mapped on X chromosome within a region of about 0.6 map unit, but has not been cloned so far. We are trying to clone it by cosmid rescue. If
sma-5 is identified, we will inject it into the wild-type nematode to see whether the transgenic nematode is larger than wild type.