Transient morphogenetic constraints organize self-assembling axon neighborhoods for robust yet flexible wiring
- 1Memorial Sloan Kettering Cancer Center
Abstract
Nervous systems form wiring patterns that are reproducible across individuals. This reproducibility is thought to emerge from molecular encoding and developmental events, but their relative contributions remain unclear. We address this question in the C. elegans neuropil, where embryonic developmental dynamics and adult anatomy are resolved at single-cell resolution. We find that transient morphogenetic structures -- rosettes, corridor cells, pioneer axon scaffold -- restrict which axons make contact, shaping the neuropil into overlapping neighborhoods. This demonstrates how early events constrain wiring choices, but not whether they explain the resulting reproducibility. To explain, we use an agent-based model of stochastic innervation that recapitulates macro- and micro-level reproducibility, revealing a trade-off between physical constraint and molecular specificity that limits neighborhood size. Counterintuitively, less selective axons produce more reproducible wiring when constrained within neighborhoods. This trade-off lets nervous systems maximize reproducibility without having to molecularly encode every axon-contact, a strategy for robust yet flexible wiring.
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BibTeX
@misc{brittin2026transient,
title = {{Transient morphogenetic constraints organize self-assembling axon neighborhoods for robust yet flexible wiring}},
author = {C. Brittin and A. Santella and K. M. Barnes and M. Moyle and L. Fan and R. Christensen and I. Kolotuev and W. Mohler and H. Shroff and D. Colon-Ramos and Z. Bao},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.750528},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.750528v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Transient morphogenetic constraints organize self-assembling axon neighborhoods for robust yet flexible wiring
AU - C. Brittin
AU - A. Santella
AU - K. M. Barnes
AU - M. Moyle
AU - L. Fan
AU - R. Christensen
AU - I. Kolotuev
AU - W. Mohler
AU - H. Shroff
AU - D. Colon-Ramos
AU - Z. Bao
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.750528
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.750528v1
AB - Nervous systems form wiring patterns that are reproducible across individuals. This reproducibility is thought to emerge from molecular encoding and developmental events, but their relative contributions remain unclear. We address this question in the C. elegans neuropil, where embryonic developmental dynamics and adult anatomy are resolved at single-cell resolution. We find that transient morphogenetic structures -- rosettes, corridor cells, pioneer axon scaffold -- restrict which axons make contact, shaping the neuropil into overlapping neighborhoods. This demonstrates how early events constrain wiring choices, but not whether they explain the resulting reproducibility. To explain, we use an agent-based model of stochastic innervation that recapitulates macro- and micro-level reproducibility, revealing a trade-off between physical constraint and molecular specificity that limits neighborhood size. Counterintuitively, less selective axons produce more reproducible wiring when constrained within neighborhoods. This trade-off lets nervous systems maximize reproducibility without having to molecularly encode every axon-contact, a strategy for robust yet flexible wiring.
ER -