Atypical TGF-β Signaling Controls Neuronal Guidance inCaenorhabditis elegans

Abstract

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-β) type I receptor SMA-6 (small-6) acts independently of its cognate TGF-β type II receptor DAF-4 (dauer formation-defective-4) to control neuronal guidance. SMA-6 directs neuronal development from the epidermis through interactions with three, orphan, TGF-β 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-β-mediated regulatory mechanism to ensure correct development of the nervous system.

Reciprocal interactions between transforming growth factor beta signaling and collagens: Insights from Caenorhabditis elegans

“…The C. elegans genome contains five genes encoding TGF-β-related ligands: daf-7, dbl-1, tig-2, tig-3, and unc-129. Three genes, tig-2, tig-3, and unc-129, are linked to axon guidance in C. elegans [23][24][25] and will not be discussed in detail here. Two genes, daf-7 and dbl-1, encode canonical TGF-β-related ligands and have well-characterized functions and signaling pathways (Figure 1).…”