A TGFb -related signaling pathway regulates body size and male tail morphogenesis in C. elegans. Mutations in
dbl-1 ligand,
sma-6 type I receptor,
daf-4 type II receptor, and
sma-2,
sma-3, and
sma-4 Smads result in similar defects. Mutants hatch at about the same size as wild type, but grow more slowly and are half the normal size at adulthood. In the male tail, defects in morphogenesis and patterning result in crumpled spicules and sensory ray fusions. In addition, mutants show less frequent expression of dopamine in sensory neurons in rays 5, 7, and 9, the same rays that are involved in ray fusions and changes in morphology. In a genetic screen for additional Small mutants (C.S.D. and R.W.Padgett, unpublished), four alleles of a novel gene
sma-9 were isolated.
sma-9 mutants have defects in all of the tissues described above, but in each case, the
sma-9 phenotype differs slightly from that of the other mutants. In body size, L1 and L2
sma-9 animals have the same size and growth rate as TGFb Sma mutants, but after this time, their growth rate increases to a wild-type rate. In the male tail,
sma-9 animals have crumpled spicules, but at a lower penetrance. Sensory ray fusions are seen between rays 8 and 9, but never between rays 4 and 5 or rays 6 and 7. Four
sma-9 alleles from a noncomplementation screen show the same ray and spicule phenotypes. Finally, the frequency of dopamine expression in neurons of rays 5, 7, and 9 is reduced, but unlike in the TGFb Sma mutants, the levels of expression are also reduced in neurons that still express the neurotransmitter. Based on the phenotypic analysis, we suggest that
sma-9 is a co-factor or modulator of the TGFb pathway. To understand better how
sma-9 interacts with the signaling pathway, we are analyzing double mutants between
sma-9 and TGFb Sma mutants. Surprisingly, the phenotype of
sma-3;
sma-9 doubles is less severe than that of
sma-3 alone. We have also initiated a molecular analysis of
sma-9. After mapping
sma-9 X, we obtained transformation rescue with the cosmid C44C10. Progress in identifying the
sma-9 open reading frame will be presented.