{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:41:00Z","timestamp":1777999260380,"version":"3.51.4"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science (JSPS) KAKENHI","award":["20K08224"],"award-info":[{"award-number":["20K08224"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Dendritic spine formation\/maintenance is highly dependent on actin cytoskeletal dynamics, which is regulated by small GTPases Rac1 and Cdc42 through their downstream p21-activated kinase\/LIM-kinase-I\/cofilin pathway. ARHGEF7, also known as \u00df-PIX, is a guanine nucleotide exchange factor for Rac1 and Cdc42, thereby activating Rac1\/Cdc42 and the downstream pathway, leading to the upregulation of spine formation\/maintenance. We found that STIL, one of the primary microcephaly gene products, is associated with ARHGEF7 in dendritic spines and that knockdown of Stil resulted in a significant reduction in dendritic spines in neurons both in vitro and in vivo. Rescue experiments indicated that the STIL requirement for spine formation\/maintenance depended on its coiled coil domain that mediates the association with ARHGEF7. The overexpression of Rac1\/Cdc42 compensated for the spine reduction caused by STIL knockdown. FRET experiments showed that Rac activation is impaired in STIL knockdown neurons. Chemical long-term potentiation, which triggers Rac activation, promoted STIL accumulation in the spine and its association with ARHGEF7. The dynamics of these proteins further supported their coordinated involvement in spine formation\/maintenance. Based on these findings, we concluded that the centrosomal protein STIL is a novel regulatory factor essential for spine formation\/maintenance by activating Rac and its downstream pathway, possibly through the association with ARHGEF7.<\/jats:p>","DOI":"10.3390\/cells14020062","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T05:06:34Z","timestamp":1736226394000},"page":"62","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The MCPH7 Gene Product STIL Is Essential for Dendritic Spine Formation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1832-2406","authenticated-orcid":false,"given":"Tohru","family":"Matsuki","sequence":"first","affiliation":[{"name":"Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3324-5998","authenticated-orcid":false,"given":"Hidenori","family":"Tabata","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pathology, Aichi Medical University School of Medicine, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6827-8434","authenticated-orcid":false,"given":"Koh-ichi","family":"Nagata","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurobiology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Aichi, Japan"},{"name":"Department of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2373-2752","authenticated-orcid":false,"given":"Yumi","family":"Tsuneura","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shima","family":"Eda","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6566-9483","authenticated-orcid":false,"given":"Kenji","family":"Kasai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Aichi Medical University School of Medicine, Nagakute 480-1195, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1444-0800","authenticated-orcid":false,"given":"Atsuo","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Institute for Developmental Research, Aichi Developmental Disability Center, Kasugai 480-0392, Aichi, Japan"},{"name":"Department of Neurochemistry, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Aichi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.neuron.2017.08.008","article-title":"Spine Dynamics: Are They All the Same?","volume":"96","author":"Berry","year":"2017","journal-title":"Neuron"},{"key":"ref_2","first-page":"319","article-title":"Neue darstellung vom histologischen bau des centralnervensystem","volume":"3","year":"1893","journal-title":"Arch. 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