{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T08:05:08Z","timestamp":1789286708972,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,12]]},"group-title":"Neuroscience","reference-count":0,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["R24-OD016474"],"award-info":[{"award-number":["R24-OD016474"]}]},{"name":"NIH","award":["R01GM152927"],"award-info":[{"award-number":["R01GM152927"]}]},{"name":"NIH","award":["R01NS076558"],"award-info":[{"award-number":["R01NS076558"]}]},{"name":"NIH","award":["DP1NS111778"],"award-info":[{"award-number":["DP1NS111778"]}]},{"name":"NIH","award":["F32-NS098616"],"award-info":[{"award-number":["F32-NS098616"]}]},{"name":"NIH","award":["P30CA008748"],"award-info":[{"award-number":["P30CA008748"]}]},{"name":"Chan Zuckerberg Initiative and the Silicon Valley Community Foundation","award":["2019-198110 (5022)"],"award-info":[{"award-number":["2019-198110 (5022)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,12]]},"abstract":"<jats:p>\n                  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\n                  <jats:italic>C. elegans<\/jats:italic>\n                  neuropil, where embryonic developmental dynamics and adult anatomy are resolved at single-cell resolution. We find that transient morphogenetic structures \u2014 rosettes, corridor cells, pioneer axon scaffold \u2014 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.\n                <\/jats:p>","DOI":"10.64898\/2026.09.09.750528","type":"posted-content","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T07:55:16Z","timestamp":1789286116000},"source":"Crossref","is-referenced-by-count":0,"title":["Transient morphogenetic constraints organize self-assembling axon neighborhoods for robust yet flexible wiring"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1143-554X","authenticated-orcid":false,"given":"Christopher","family":"Brittin","sequence":"first","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Santella","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2546-9529","authenticated-orcid":false,"given":"Kristopher M.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine, MSKCC;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8609-0164","authenticated-orcid":false,"given":"Mark","family":"Moyle","sequence":"additional","affiliation":[{"name":"Brigham Young University-Idaho;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Fan","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Christensen","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1433-8048","authenticated-orcid":false,"given":"Irina","family":"Kolotuev","sequence":"additional","affiliation":[{"name":"University of Lausanne;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-547X","authenticated-orcid":false,"given":"William","family":"Mohler","sequence":"additional","affiliation":[{"name":"University of Connecticut Health Center;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari","family":"Shroff","sequence":"additional","affiliation":[{"name":"Janelia Research Campus, Howard Hughes Medical Institute;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0223-7717","authenticated-orcid":false,"given":"Daniel","family":"Col\u00f3n-Ramos","sequence":"additional","affiliation":[{"name":"Yale University;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2201-2745","authenticated-orcid":false,"given":"Zhirong","family":"Bao","sequence":"additional","affiliation":[{"name":"Southern University of Science and Technology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.09.750528","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T07:55:16Z","timestamp":1789286116000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.09.750528"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":0,"URL":"https:\/\/doi.org\/10.64898\/2026.09.09.750528","relation":{},"subject":[],"published":{"date-parts":[[2026,9,12]]},"subtype":"preprint"}}