{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:34:58Z","timestamp":1768509298775,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,2]]},"group-title":"Developmental Biology","reference-count":106,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,4]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  The\n                  <jats:italic>C. elegans<\/jats:italic>\n                  hermaphrodite distal tip cell (DTC) leads gonadogenesis. Loss-of-function mutations in a\n                  <jats:italic>C. elegans<\/jats:italic>\n                  ortholog of the Rac1 GTPase (\n                  <jats:italic>ced-10<\/jats:italic>\n                  ) and its GEF complex (\n                  <jats:italic>ced-5<\/jats:italic>\n                  \/DOCK180,\n                  <jats:italic>ced-2<\/jats:italic>\n                  \/CrkII,\n                  <jats:italic>ced-12<\/jats:italic>\n                  \/ELMO) cause gonad migration defects related to directional sensing; we discovered an additional defect class of gonad bifurcation in these mutants. Using genetic approaches, tissue-specific and whole-body RNAi, and\n                  <jats:italic>in vivo<\/jats:italic>\n                  imaging of endogenously tagged proteins and marked cells, we find that loss of Rac1 or its regulators causes the DTC to fragment as it migrates. Both products of fragmentation\u2014the now-smaller DTC and the membranous patch of cellular material\u2014localize important stem cell niche signaling (LAG-2\/DSL ligand) and migration (INA-1\/integrin subunit alpha) factors to their membranes, but only one retains the DTC nucleus and therefore the ability to maintain gene expression over time. The enucleate patch can lead a bifurcating branch off the gonad arm that grows through germ cell proliferation. Germ cells in this branch differentiate as the patch loses LAG-2 expression. While the nucleus is surprisingly dispensable for aspects of leader cell function, it is required for stem cell niche activity long-term. Prior work found that\n                  <jats:italic>\n                    Rac1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ;Rac2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  mouse erythrocytes fragment; in this context, our new findings support the conclusion that maintaining a cohesive but deformable cell is a conserved function of this important cytoskeletal regulator.\n                <\/jats:p>","DOI":"10.1101\/2023.12.01.569642","type":"posted-content","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T04:35:15Z","timestamp":1701491715000},"source":"Crossref","is-referenced-by-count":0,"title":["Getting there in one piece: The Rac pathway prevents cell fragmentation in a nonprotrusively migrating leader cell during organogenesis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5944-9924","authenticated-orcid":false,"given":"Noor","family":"Singh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen Jian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0967-4020","authenticated-orcid":false,"given":"Kacy Lynn","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023120703300678000_2023.12.01.569642v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(81)90284-0"},{"key":"2023120703300678000_2023.12.01.569642v2.2","unstructured":"Lehmann, R. 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