{
  "abstract": "Proper assembly of cortical circuits depends on the orderly migration of excitatory projection neurons, a multistep process marked by dynamic cell shape remodeling, including the transition from multipolar-to-bipolar morphology (MP-to-BP) followed by radial glial-guided locomotion. Although molecular players regulating individual stages have been identified, how these steps are coordinated remains unclear. Here, we uncover a critical role for the multidomain Rho-GAP oligophrenin-1 (OPHN1), an X-linked intellectual disability protein, as a dual-function regulator of radial migration. Using a molecular replacement strategy combined with live-cell imaging, we show that OPHN1 governs successive phases of migration through distinct domains and mechanisms: its GAP domain promotes the MP-to-BP transition by suppressing RHOA-ROCK signaling, whereas its second proline-rich domain regulates leading process remodeling and nucleokinesis during locomotion via interaction with the protein kinase C and casein kinase substrate in neurons 2 (PACSIN2). Together, these findings reveal a previously unrecognized role for OPHN1 in early cortical development and demonstrate that its domain-specific functions facilitate stepwise control of radial migration during corticogenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA",
    "Montreal Clinical Research Institute (IRCM), Université de Montréal, Montréal, QC H2W 1R7, Canada",
    "Department of Pathology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Francesco Boato"
    },
    {
      "affs": [
        0
      ],
      "name": "Benjamin de la Cruz Thea"
    },
    {
      "affs": [
        0
      ],
      "name": "Shanu George"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu-Ting Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Chia-Lin Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Sarah Nahlé"
    },
    {
      "affs": [
        2
      ],
      "name": "Justyna A. Janas"
    },
    {
      "affs": [
        1
      ],
      "name": "Jean-François Coté"
    },
    {
      "affs": [
        0
      ],
      "name": "Linda Van Aelst"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/40vbz4tka0g6j.bib",
  "cited_by": 0,
  "doi": "10.1101/gad.354125.126",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726877/",
  "id": "40vbz4tka0g6j",
  "issns": [
    "0890-9369",
    "1549-5477"
  ],
  "landing_url": "https://doi.org/10.1101/gad.354125.126",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2806|Neurogenesis and neuroplasticity mechanisms"
    ]
  ],
  "openalex": "W7224437259",
  "pdf_url": null,
  "pmcid": "PMC13726877",
  "pmid": "42957276",
  "published": "2026-10-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/40vbz4tka0g6j.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:23:06Z",
      "native_id": "PMC13726877",
      "source": "pmc",
      "url": "https://doi.org/10.1101/gad.354125.126"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Neurogenesis and neuroplasticity mechanisms",
      "subfield": "neuroscience"
    }
  ],
  "title": "Distinct domains of Oligophrenin-1 regulate successive phases of cortical radial migration via RhoA- and Pacsin2-dependent mechanisms",
  "title_text": "Distinct domains of Oligophrenin-1 regulate successive phases of cortical radial migration via RhoA- and Pacsin2-dependent mechanisms",
  "type": "preprint",
  "updated_at": "2026-11-06T12:22:42Z",
  "url": "https://research.draconitic.com/paper/40vbz4tka0g6j",
  "venue": "Genes & development",
  "versions": []
}