Transforming growth factor b (TGFb) growth factors control cell fate by regulating the expression of genes encoding cell-cycle regulators, differentiation factors, cell-adhesion molecules and many other components that are key determinants of cell phenotype. In C. elegans, identified components of this signaling pathway include:
sma-2,
sma-3, and
sma-4 which are members of a conserved family of TGFbsignal transducers, the Smads which function downstream of TGFb receptors (1), the type I receptor
sma-6 (2) and the type II receptor
daf-4 (3). Biochemical studies on the vertebrate Smads has led to a model in which Smads has led to a model in which Smad proteins are activated by phosphorylation by TGFb receptors allowing them to translocate to the nucleus and act as transcriptional activators. There is a continued interest in identifying novel components of this signaling pathway. One of the newest member of this pathway that has been identified is
sma-9. The reason that
sma-9 may be a component of this family is: it affects body size (making it small) which is a classical Sma phenotype; and male tail patterning (in such ways as fusion of rays); other TGFb signaling mutants have similar phenotypic effects. As in existing sma mutants,
sma-9(
wk62) mutants show fusions of rays 8 and 9 ~40% of the time. Unlike existing mutants, however,
sma-9 does not have frequent fusions of rays 4, 5, 6, and 7. Our goal is to characterize
sma-9. To characterize
sma-9, it is necessary to know what it encodes and that will be useful in finding out how
sma-9 works in TGFb signaling. Sma-9 maps to the X chromosome, but not near any known TGFbsignaling components. So it is likely to be a previously unknown component of this pathway. In order to characterize
sma-9, we will refine its map position. First, we will determine the recombination frequency relative to the following known genes:
unc-1 mec-2 or
unc-2 mec-7. Second, the male tail phenotype will be better described. It will be necessary to produce double mutants using
him-5 (high incidence of males) to increase the frequency of males. Nomarski differential interference contrast microscopy at X400 magnification will be used to examine the defects in ray pattern in males. Finally, we have begun to characterize the interaction of
sma-9 with known TGFb signaling genes by constructing and analyzing double mutants. (1) Savage et al., PNAS, 1996. (2) S. Krishna and R.W. Padgett, personal communication (3) Estevez et al., Nature, 1993.