In Caenorhabditis elegans, two well-characterized TGF beta signaling cascades have been identified: the Small/Male tail abnormal (Sma/Mab) and Dauer formation (Daf) pathways. The Sma/Mab pathway regulates body size morphogenesis and male tail development. The ligand of the pathway,
dbl-1, transmits its signal through two receptor serine threonine kinases,
daf-4 and
sma-6, which in turn regulate the activity of the Smads,
sma-2,
sma-3, and
sma-4. In general, Smads have been shown to both positively and negatively regulate the transcriptional activity of downstream target genes in various organisms. In C. elegans, however, target genes have remained elusive. We have cloned and characterized
lon-1, a gene with homology to the cysteine-rich secretory protein (CRISP) family of proteins.
lon-1 regulates body size morphogenesis, but does not affect male tail development.
lon-1 is expressed in hypodermal tissues, which is the focus of body size determination, similar to
sma-2,
sma-4, and
sma-6. Using genetic methods, we show that
lon-1 lies downstream of the Sma/Mab signaling cascade and demonstrate that
lon-1 mRNA levels are up-regulated in
sma-6-null mutant animals. This provides evidence that
lon-1 is negatively regulated by Sma/Mab pathway signaling. Taken together, these data identify
lon-1 as a novel downstream target gene of the
dbl-1 TGF beta-like signaling pathway.