{
  "abstract": "Precise regulation of early cortical development is essential for the establishment of normal brain function, and its disruption can contribute to the pathogenesis of neurodevelopmental disorders (NDDs). Impaired motor function is a prominent early manifestation of various NDDs, yet the mechanisms remain elusive. Here, we identified ARHGEF1, a Rho family guanine nucleotide exchange factor highly expressed during early corticogenesis, as a novel regulator in embryonic cortical neurogenesis and adult motor function. By Emx1‐Cre‐mediated forebrain deletion of Arhgef1 in mice (Arhgef1 cKO mice), early cortical neurogenesis is specifically disrupted, leading to reduced deep‐layer cortical neurons. Mechanistically, Arhgef1 deficiency overactivates RAC1/CDC42‐PAK1‐Cofilin signaling in early cortical development, whereas pharmacological PAK1 inhibition within this critical window rescues the genesis of deep‐layer cortical neurons. Importantly, Arhgef1 cKO mice exhibit remarkable motor learning and coordination deficits in adulthood, accompanied by altered neuronal morphology in the motor cortex and impaired neuronal activities in motor circuits. In all, we elucidate a critical developmental window when ARHGEF1 governs corticogenesis via negatively regulates PAK1‐dependent pathway and further reveal an important role for ARHGEF1 in maintaining normal motor function in adulthood.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Bioactive Molecules and Druggability Assessment Guangdong Basic Research Center of Excelence for Natural Bioactive Molecules and Discovery of Innovative Drugs Jinan University Guangzhou China",
    "JNU‐HKUST Joint Laboratory for Neuroscience and Innovative Drug Research Guangdong Hong Kong‐Macau Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research Jinan University Guangzhou China",
    "Department of Pharmacy Zhujiang Hospital Southern Medical University Guangzhou China",
    "Department of Pharmacy School of Medicine the Sixth Affiliated Hospital of South China University of Technology (Nanhai District People's Hospital of Foshan) Foshan China",
    "Guangdong‐Hong Kong‐Macau Institute of CNS Regeneration Key Laboratory of CNS Regeneration (Ministry of Education) Jinan University Guangzhou China",
    "School of Biomedical Sciences and Gerald Choa Neuroscience Institute The Chinese University of Hong Kong Hong Kong China",
    "Neurological Research Institute of Integrated Traditional Chinese and Western Medicine First School of Clinical Medicine The First Affiliated Hospital Guangdong Pharmaceutical University Guangzhou China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Liuren Li",
      "orcid": "0000-0002-0568-0602"
    },
    {
      "affs": [
        3
      ],
      "name": "Xuanyue Ma",
      "orcid": "0000-0003-1488-1366"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhenyu Ding"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bang Sun"
    },
    {
      "affs": [
        4
      ],
      "name": "Linglin Liu"
    },
    {
      "affs": [
        5
      ],
      "name": "Hei Matthew Yip",
      "orcid": "0000-0002-5203-1138"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Wei Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tianying Wu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuan Guo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yinghui Peng"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shiqing Zhang",
      "orcid": "0000-0002-0785-5461"
    },
    {
      "affs": [
        5
      ],
      "name": "Jacque Pak Kan Ip",
      "orcid": "0000-0003-4545-8261"
    },
    {
      "affs": [
        4
      ],
      "name": "Li Zhang",
      "orcid": "0000-0003-1489-0879"
    },
    {
      "affs": [
        6
      ],
      "name": "Keshen Li",
      "orcid": "0000-0003-2389-7706"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lei Shi",
      "orcid": "0000-0001-8695-3432"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/csgyv7dy4ta3r.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78426",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696771/",
  "id": "csgyv7dy4ta3r",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.78426",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2806|Neurogenesis and neuroplasticity mechanisms"
    ]
  ],
  "openalex": "W7223570243",
  "pdf_url": "https://europepmc.org/articles/PMC13696771?pdf=render",
  "pmcid": "PMC13696771",
  "pmid": "42928451",
  "published": "2026-10-25",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/csgyv7dy4ta3r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:04Z",
      "native_id": "PMC13696771",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.78426"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928451",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928451"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Neurogenesis and neuroplasticity mechanisms",
      "subfield": "neuroscience"
    }
  ],
  "title": "Arhgef1 Deletion Disrupts Early Cortical Neurogenesis via PAK1 Overactivation and Causes Motor Dysfunction in Adulthood",
  "title_text": "Arhgef1 Deletion Disrupts Early Cortical Neurogenesis via PAK1 Overactivation and Causes Motor Dysfunction in Adulthood",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:03Z",
  "url": "https://research.draconitic.com/paper/csgyv7dy4ta3r",
  "venue": "Advanced Science",
  "versions": []
}