{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:59:21Z","timestamp":1791377961178,"version":"4.3.2"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing, China","doi-asserted-by":"publisher","award":["cstc2021jcyj-msxmX0563"],"award-info":[{"award-number":["cstc2021jcyj-msxmX0563"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cell adhesion molecules (CAMs) are critical regulators of neural wiring that guide axon targeting, dendritic arborization, and synaptic connections. Although individual neurons express diverse CAMs, the integrated regulatory roles of these molecules remain largely unclear. We identified 3 CAMs, N-Cadherin (CadN), immunoglobulin superfamily members DIP-\u03b1, and Klingon (Klg), which are coexpressed in Drosophila amacrine neuron Dm12 in the visual system, exploring how they synergistically regulate the precise wiring of Dm12 neurons. Using single-cell MARCM clones and developmental time-course analyses, we showed that CadN and DIP-\u03b1 cooperate in parallel pathways to promote layer-specific axon targeting and dendritic elaboration. Simultaneous loss of both CAMs yielded more severe defects of axon mistargeting and dendritic field size reduction compared with single mutants. Conversely, loss of klg triggered expansion of the dendritic field, which caused a proportional scaling of total synapse number while maintaining normal synaptic density. Both loss and overexpression of klg caused an expansion of dendritic coverage, indicating that Dm12 dendritic arborization was highly sensitive to homeostatic Klg levels. Finally, we found that dendritic expansion via klg manipulation significantly suppressed the axon mistargeting ratio of DIP-\u03b1 mutants and alleviated the severity of targeting defects in CadN mutants. Furthermore, loss of either DIP-\u03b1 or CadN significantly reduced the expansion of dendritic coverage in klg mutant Dm12, resulting in intermediate dendritic field sizes. In summary, our work highlighted how multiple CAMs with opposing regulatory roles functioned synergistically to fine-tune neurite morphogenesis during neural circuits assembly.<\/jats:p>","DOI":"10.1093\/genetics\/iyag225","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:12:55Z","timestamp":1787656375000},"source":"Crossref","is-referenced-by-count":0,"title":["Cell adhesion molecules\n                    <i>CadN<\/i>\n                    ,\n                    <i>DIP-\u03b1<\/i>\n                    , and\n                    <i>klg<\/i>\n                    regulate axon targeting and dendritic elaboration through synergistic and opposing effects"],"prefix":"10.1093","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4997-9717","authenticated-orcid":false,"given":"Xinyu","family":"Ren","sequence":"first","affiliation":[{"name":"School of Life Sciences, Genetic Engineering Research Center, Chongqing University , Chongqing 401331 ,","place":["China"]},{"name":"Chongqing Engineering Research Center for Fungal Insecticide , Chongqing 401331 ,","place":["China"]},{"name":"Key Laboratory of Gene Function and Regulation Technologies under Chongqing Municipal Education Commission , Chongqing 401331 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3253-3951","authenticated-orcid":false,"given":"Qi","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Genetic Engineering Research Center, Chongqing University , Chongqing 401331 ,","place":["China"]},{"name":"Chongqing Engineering Research Center for Fungal Insecticide , Chongqing 401331 ,","place":["China"]},{"name":"Key Laboratory of Gene Function and Regulation Technologies under Chongqing Municipal Education Commission , Chongqing 401331 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"2026100708032616000_iyag225-B1","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1242\/dev.124.4.781","article-title":"Klingon, a novel member of the Drosophila immunoglobulin superfamily, is required for the development of the R7 photoreceptor neuron","volume":"124","author":"Butler","year":"1997","journal-title":"Development"},{"key":"2026100708032616000_iyag225-B2","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1016\/j.cell.2015.11.022","article-title":"Control of synaptic connectivity by a network of Drosophila IgSF cell surface proteins","volume":"163","author":"Carrillo","year":"2015","journal-title":"Cell"},{"key":"2026100708032616000_iyag225-B3","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.neuron.2017.04.011","article-title":"Conditional deletion of all neurexins defines diversity of essential synaptic organizer functions for neurexins","volume":"94","author":"Chen","year":"2017","journal-title":"Neuron"},{"key":"2026100708032616000_iyag225-B4","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.neuron.2013.12.021","article-title":"Cell-type-specific labeling of synapses in vivo through synaptic tagging with recombination","volume":"81","author":"Chen","year":"2014","journal-title":"Neuron"},{"key":"2026100708032616000_iyag225-B5","doi-asserted-by":"publisher","first-page":"9837","DOI":"10.1073\/pnas.1818631116","article-title":"Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence","volume":"116","author":"Cheng","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026100708032616000_iyag225-B6","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/nrn.2015.3","article-title":"Specification of synaptic connectivity by cell surface interactions","volume":"17","author":"De Wit","year":"2016","journal-title":"Nat Rev Neurosci"},{"key":"2026100708032616000_iyag225-B7","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.cell.2013.08.059","article-title":"An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis","volume":"155","author":"Dong","year":"2013","journal-title":"Cell"},{"key":"2026100708032616000_iyag225-B8","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1007\/BF00218858","article-title":"The optic lobe of Drosophila melanogaster. 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