{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:29:59Z","timestamp":1772155799828,"version":"3.50.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T00:00:00Z","timestamp":1681344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) encodes tens of thousands of cell recognition molecules via alternative splicing, which are required for neural function. A canonical self-avoidance model seems to provide a central mechanistic basis for Dscam1 functions in neuronal wiring. Here, we reveal extensive noncanonical functions of Dscam1 isoforms in neuronal wiring. We generated a series of allelic cis mutations in Dscam1, encoding a normal number of isoforms, but with an altered isoform composition. Despite normal dendritic self-avoidance and self-\/nonself-discrimination in dendritic arborization (da) neurons, which is consistent with the canonical self-avoidance model, these mutants exhibited strikingly distinct spectra of phenotypic defects in the three types of neurons: up to \u223c60% defects in mushroom bodies, a significant increase in branching and growth in da neurons, and mild axonal branching defects in mechanosensory neurons. Remarkably, the altered isoform composition resulted in increased dendrite growth yet inhibited axon growth. Moreover, reducing Dscam1 dosage exacerbated axonal defects in mushroom bodies and mechanosensory neurons but reverted dendritic branching and growth defects in da neurons. This splicing-tuned regulation strategy suggests that axon and dendrite growth in diverse neurons cell-autonomously require Dscam1 isoform composition. These findings provide important insights into the functions of Dscam1 isoforms in neuronal wiring.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgad135","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T06:41:29Z","timestamp":1681368089000},"source":"Crossref","is-referenced-by-count":5,"title":["<i>Cis<\/i>\n                    mutagenesis in vivo reveals extensive noncanonical functions of Dscam1 isoforms in neuronal wiring"],"prefix":"10.1093","volume":"2","author":[{"given":"Shixin","family":"Zhang","sequence":"first","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4466-4047","authenticated-orcid":false,"given":"Xi","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041 , People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2364-6448","authenticated-orcid":false,"given":"Haiyang","family":"Dong","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4366-5702","authenticated-orcid":false,"given":"Bingbing","family":"Xu","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1285-4789","authenticated-orcid":false,"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6075-5454","authenticated-orcid":false,"given":"Ying","family":"Fu","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6247-1786","authenticated-orcid":false,"given":"Yiwen","family":"Du","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-8741","authenticated-orcid":false,"given":"Yanda","family":"Zhu","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9019-2154","authenticated-orcid":false,"given":"Jilong","family":"Shi","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Shi","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6509-1765","authenticated-orcid":false,"given":"Jianhua","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Insect Sciences, Zhejiang University , Hangzhou ZJ310058 , People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-6267","authenticated-orcid":false,"given":"Haihuai","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041 , People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7125-7055","authenticated-orcid":false,"given":"Yongfeng","family":"Jin","sequence":"additional","affiliation":[{"name":"MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, College of Life Sciences, Zhejiang University , Hangzhou ZJ310058 , People's Republic of 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