Atypical TGF-beta signaling controls neuronal guidance in Caenorhabditis elegans

Coordinated expression of cell adhesion and signaling molecules is crucial for brain development. Here, we report that the Caenorhabditis elegans transforming growth factor beta (TGF-beta) type I receptor SMA-6 (small-6) acts independently of its cognate TGF-beta type II receptor DAF-4 (dauer formation-defective-4) to control neuronal guidance. SMA-6 directs neuronal development from the hypodermis through interactions with three, orphan, TGF-beta ligands. Intracellular signaling downstream of SMA-6 limits expression of NLR-1, an essential Neurexin-like cell adhesion receptor, to enable neuronal guidance. Together, our data identify an atypical TGF-beta-mediated regulatory mechanism to ensure correct neuronal development.