Neph1-Robo mechanical anchoring stabilizes neurite branch orientation independently of receptor-specific intracellular signaling
Abstract
Neurite morphogenesis is classically viewed as a signal-driven process in which extracellular cues activate intracellular pathways to direct growth. Here, we identify a distinct mechanism in which adhesion preserves neurite architecture independently of canonical receptor signaling. Using axonal branching in Caenorhabditis elegans PVP interneurons, we show that neuronal SYG-1/Neph1 and epithelial SAX-3/Robo establish a transcellular interface that stabilizes branch orientation and may help resist physiological tissue deformation. This stabilization requires SYG-1 membrane tethering and extracellular domains, but not its cytoplasmic signaling domain, and can be reconstituted with cytoplasmically truncated SYG-1 and SAX-3. The canonical Robo ligand SLT-1 is required for this anchoring mechanism and promotes SYG-1/SAX-3-dependent cell association in vitro. Moreover, an unrelated synthetic adhesion pair partially substitutes for the native receptors and restores branch orientation. These findings reveal a signaling-independent structural role for classical guidance receptors in stabilizing neurite architecture within a deforming tissue environment.
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BibTeX
@misc{lin2026neph1robo,
title = {{Neph1-Robo mechanical anchoring stabilizes neurite branch orientation independently of receptor-specific intracellular signaling}},
author = {Yun-Hsien Lin and Chun-Hao Chen},
howpublished = {Research Square},
year = {2026},
month = oct,
doi = {10.21203/rs.3.rs-11121715/v1},
url = {https://doi.org/10.21203/rs.3.rs-11121715/v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Neph1-Robo mechanical anchoring stabilizes neurite branch orientation independently of receptor-specific intracellular signaling
AU - Yun-Hsien Lin
AU - Chun-Hao Chen
PY - 2026
DA - 2026/10/14
PB - Research Square
DO - 10.21203/rs.3.rs-11121715/v1
UR - https://doi.org/10.21203/rs.3.rs-11121715/v1
AB - Neurite morphogenesis is classically viewed as a signal-driven process in which extracellular cues activate intracellular pathways to direct growth. Here, we identify a distinct mechanism in which adhesion preserves neurite architecture independently of canonical receptor signaling. Using axonal branching in Caenorhabditis elegans PVP interneurons, we show that neuronal SYG-1/Neph1 and epithelial SAX-3/Robo establish a transcellular interface that stabilizes branch orientation and may help resist physiological tissue deformation. This stabilization requires SYG-1 membrane tethering and extracellular domains, but not its cytoplasmic signaling domain, and can be reconstituted with cytoplasmically truncated SYG-1 and SAX-3. The canonical Robo ligand SLT-1 is required for this anchoring mechanism and promotes SYG-1/SAX-3-dependent cell association in vitro. Moreover, an unrelated synthetic adhesion pair partially substitutes for the native receptors and restores branch orientation. These findings reveal a signaling-independent structural role for classical guidance receptors in stabilizing neurite architecture within a deforming tissue environment.
SN - 2693-5015
ER -