{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:09:29Z","timestamp":1793833769520,"version":"4.6.1"},"reference-count":37,"publisher":"The Company of Biologists","issue":"1","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIGMS 3T32GM007309"],"award-info":[{"award-number":["NIGMS 3T32GM007309"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["U54CA268083"],"award-info":[{"award-number":["U54CA268083"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Foundation","award":["1915491"],"award-info":[{"award-number":["1915491"]}]},{"DOI":"10.13039\/100001006","name":"Breast Cancer Research Foundation","doi-asserted-by":"crossref","award":["BCRF-20-048"],"award-info":[{"award-number":["BCRF-20-048"]}],"id":[{"id":"10.13039\/100001006","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Johns Hopkins University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Branched epithelial networks are generated through an iterative process of elongation and bifurcation. We sought to understand bifurcation of the mammary epithelium. To visualize this process, we utilized three-dimensional (3D) organotypic culture and time-lapse confocal microscopy. We tracked cell migration during bifurcation and observed local reductions in cell speed at the nascent bifurcation cleft. This effect was proximity dependent, as individual cells approaching the cleft reduced speed, whereas cells exiting the cleft increased speed. As the cells slow down, they orient both migration and protrusions towards the nascent cleft, while cells in the adjacent branches orient towards the elongating tips. We next tested the hypothesis that TGF-\u03b2 signaling controls mammary branching by regulating cell migration. We first validated that addition of TGF-\u03b21 (TGFB1) protein increased cleft number, whereas inhibition of TGF-\u03b2 signaling reduced cleft number. Then, consistent with our hypothesis, we observed that pharmacological inhibition of TGF-\u03b21 signaling acutely decreased epithelial migration speed. Our data suggest a model for mammary epithelial bifurcation in which TGF-\u03b2 signaling regulates cell migration to determine the local sites of bifurcation and the global pattern of the tubular network.<\/jats:p>","DOI":"10.1242\/jcs.259275","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T10:50:29Z","timestamp":1672915829000},"source":"Crossref","is-referenced-by-count":13,"title":["Collective cell migration is spatiotemporally regulated during mammary epithelial bifurcation"],"prefix":"10.1242","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9779-7754","authenticated-orcid":false,"given":"Neil M.","family":"Neumann","sequence":"first","affiliation":[{"name":"School of Medicine, Johns Hopkins University Department of Cell Biology and Center for Cell Dynamics , , Baltimore, MD 21205 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M.","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University Department of Cell Biology and Center for Cell Dynamics , , Baltimore, MD 21205 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8778-9689","authenticated-orcid":false,"given":"Robert J.","family":"Huebner","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University Department of Cell Biology and Center for Cell Dynamics , , Baltimore, MD 21205 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1964-0740","authenticated-orcid":false,"given":"Andrew J.","family":"Ewald","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University Department of Cell Biology and Center for Cell Dynamics , , Baltimore, MD 21205 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"2024090209261786300_JCS259275C1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ydbio.2009.09.024","article-title":"Morphogenesis of epithelial tubes: insights into tube formation, elongation, and elaboration","volume":"341","author":"Andrew","year":"2010","journal-title":"Dev. 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