{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:05:22Z","timestamp":1789581922159,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012303","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000}}],"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS115467"],"award-info":[{"award-number":["NS115467"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Hox genes have been broadly implicated in nervous system development, but the molecular and genetic mechanisms that act downstream of Hox factors remain to be identified. The MAB-5 antennapedia-like Hox transcription factor is both necessary and sufficient to cause posterior migration of the Q neuroblast descendants in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    . In response to MAB-5, the left-side QL descendants QL.a and QL.ap undergo a three-stage migration process, with each stage characterized by a posterior lamellipodial protrusion followed by cell body migration. The QL.ap cell differentiates into the PQR neuron posterior to the anus. Previous studies showed that the MAB-5-regulated gene\n                    <jats:italic>efn-4\/Ephrin<\/jats:italic>\n                    was required for the third and final stage of QL.ap migration, with\n                    <jats:italic>efn-4<\/jats:italic>\n                    mutation resulting in placement of PQR immediately anterior to the anus. This subtle and previously-undescribed phenotype opens the possibility that other known neuronal development genes could be involved. In this work, we screened known signaling mutants for third-stage PQR migration defects. We found that mutations in SAX-3\/Robo signaling, UNC-6\/Netrin signaling, and heparan sulfate proteoglycans (HSPGs) all displayed third-stage PQR migration defects. The effects in single mutants were weak compared to\n                    <jats:italic>efn-4<\/jats:italic>\n                    , and double mutant analysis revealed lack of genetic synergy, consistent with all of these molecules converging on a common pathway. This genetic analysis is consistent with physical interaction studies\n                    <jats:italic>in vitro<\/jats:italic>\n                    from another group that suggest that these molecules form connected communities of interacting extracellular domains, raising the possibility that they are all components of a large extracellular signaling complex required for posterior QL.ap migration. In this model, we envision that MAB-5\/Hox drives EFN-4\/Ephrin expression in QL.ap, which then seeds the formation of an extracellular signaling complex containing SAX-3\/Robo signaling, UNC-6\/Netrin signaling, and HSPGs that drives posterior lamellipodial formation and posterior migration.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1012303","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:52:29Z","timestamp":1788889949000},"page":"e1012303","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["EFN-4\/Ephrin converges with SAX-3\/Robo, UNC-6\/Netrin, and Heparan Sulfate Proteoglycan signaling to control MAB-5\/Hox-dependent posterior Q neuroblast migration in Caenorhabditis elegans"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0645-144X","authenticated-orcid":true,"given":"Vedant D.","family":"Jain","sequence":"first","affiliation":[{"name":"The University of Kansas","place":["Lawrence, Kansas, United States of America"],"department":["Department of Molecular Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Johannesen","sequence":"additional","affiliation":[{"name":"Computational Chemical Biology and Molecular Modeling Core Laboratory, The University of Kansas","place":["Lawrence, Kansas, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5689-7556","authenticated-orcid":true,"given":"Felipe L.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"The University of Kansas","place":["Lawrence, Kansas, United States of America"],"department":["Department of Molecular Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6819-4815","authenticated-orcid":true,"given":"Erik A.","family":"Lundquist","sequence":"additional","affiliation":[{"name":"The University of Kansas","place":["Lawrence, Kansas, United States of America"],"department":["Department of Molecular Biosciences"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"pgen.1012303.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1895\/wormbook.1.173.1","article-title":"Development and migration of the C. elegans Q neuroblasts and their descendants","author":"TC Middelkoop","year":"2014","journal-title":"WormBook"},{"issue":"2","key":"pgen.1012303.ref002","doi-asserted-by":"crossref","DOI":"10.1093\/genetics\/iyae045","article-title":"MAB-5\/Hox regulates the Q neuroblast transcriptome, including cwn-1\/Wnt, to mediate posterior migration in Caenorhabditis elegans","volume":"227","author":"VK 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