{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:04:05Z","timestamp":1772168645676,"version":"3.50.1"},"reference-count":28,"publisher":"The Company of Biologists","issue":"23","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"vor","delay-in-days":182,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01NS092062-01"],"award-info":[{"award-number":["1R01NS092062-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004856","name":"New York State Department of Health","doi-asserted-by":"publisher","award":["#C024324"],"award-info":[{"award-number":["#C024324"]}],"id":[{"id":"10.13039\/100004856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>Actin-associated proteins regulate multiple cellular processes, including proliferation and differentiation, but the molecular mechanisms underlying these processes are unclear. Here, we report that the actin-binding protein filamin A (FlnA) physically interacts with the actin-nucleating protein formin 2 (Fmn2). Loss of FlnA and Fmn2 impairs proliferation, thereby generating multiple embryonic phenotypes, including microcephaly. FlnA interacts with the Wnt co-receptor Lrp6. Loss of FlnA and Fmn2 impairs Lrp6 endocytosis, downstream Gsk3\u03b2 activity, and \u03b2-catenin accumulation in the nucleus. The proliferative defect in Flna and Fmn2 null neural progenitors is rescued by inhibiting Gsk3\u03b2 activity. Our findings thus reveal a novel mechanism whereby actin-associated proteins regulate proliferation by mediating the endocytosis and transportation of components in the canonical Wnt pathway. Moreover, the Fmn2-dependent signaling in this pathway parallels that seen in the non-canonical Wnt-dependent regulation of planar cell polarity through the Formin homology protein Daam. These studies provide evidence for integration of actin-associated processes in directing neuroepithelial proliferation.<\/jats:p>","DOI":"10.1242\/dev.139295","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T20:48:54Z","timestamp":1477601334000},"page":"4509-4520","source":"Crossref","is-referenced-by-count":37,"title":["Filamin A- and formin 2-dependent endocytosis regulates proliferation via the canonical Wnt pathway"],"prefix":"10.1242","volume":"143","author":[{"given":"Gewei","family":"Lian","sequence":"first","affiliation":[{"name":"Beth Israel Deaconess Medical Center and Harvard Medical School 1 Department of Neurology , , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Dettenhofer","sequence":"additional","affiliation":[{"name":"Central European Institute of Technology 2 , \u017derot\u00ednovo n\u00e1m. 9, Brno 601 77 , Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center and Harvard Medical School 1 Department of Neurology , , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Downing","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine 3 Department of Pathology , , Chicago, IL 60612 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjen","family":"Chenn","sequence":"additional","affiliation":[{"name":"University of Illinois College of Medicine 3 Department of Pathology , , Chicago, IL 60612 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Wong","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center and Harvard Medical School 1 Department of Neurology , , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7931-8200","authenticated-orcid":false,"given":"Volney","family":"Sheen","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center and Harvard Medical School 1 Department of Neurology , , Boston, MA 02115 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","reference":[{"key":"2024061213210149000_DEV139295C1","doi-asserted-by":"publisher","first-page":"784","DOI":"10.2741\/3957","article-title":"The Wnt signaling pathways and cell adhesion","volume":"17","author":"Amin","year":"2012","journal-title":"Front. 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