18 TGF-β Family Signaling in the Nematode C. elegans

In the nematode Caenorhabditis elegans , there are two distinct transforming growth factor-β (TGF-β) family signaling pathways with their typical core signaling components, that is, ligands, type I and type II serine-threonine kinase receptors, and Smads (Fig. 1). One of these, the dauer signaling pathway, controls an alternate third larval stage of C. elegans that forms in response to harsh environmental conditions (Riddle and Albert 1997) and feeding behavior, fat metabolism, egg laying, and thermotolerance. The other one, the body size pathway, regulates cell size, male tail development, and immunity (Patterson and Padgett 2000; Kurz and Tan 2004; Nicholas and Hodgkin 2004). DISCOVERY OF TGF-β FAMILY SIGNALING IN C. ELEGANS Genes that encode components of a TGF-β family signaling pathway were identified as mutants with defects in the regulation of the dauer decision (for a schematic presentation of the pathway, see Fig. 1B). The dauer stage is an alternate third larval stage of C. elegans (Fig. 2), in which the worm “hibernates” in response to environmental conditions that are unfavorable for growth and reproduction (Albert and Riddle 1997). Mutations in the ligand, receptors, or putative receptor-activated Smads (R-Smads) in the dauer pathway result in a dauer-constitutive phenotype, in which the worms enter and maintain growth arrest under conditions that, in wild-type worms, lead to continued growth. The first gene that was identified in the dauer pathway was daf-1 , which encodes a type I TGF-β family receptor (Georgi et al. 1990). Its identity as a TGF-β family receptor was not appreciated at...