{
  "abstract": "Human brain development depends on tightly coordinated gene-regulatory programs and the emergence of complex tissue architecture, making large scale functional interrogation difficult using conventional screen models. To overcome this challenge, we used a pooled CRISPR screening approach. Guided by neuro-specific whole-genome screens in Drosophila, we tested 129 poorly characterised human orthologs and found 8 that modify cerebral organoid development. Candidates were validated using individual CRISPR knockouts and mosaic competition assays. Among these candidates we describe FBXW11, a substrate-recognition component of the SCF E3 ubiquitin ligase complex, as a potent negative regulator of cerebral organoid expansion. FBXW11 loss increases radial glial abundance, expands ventricular-like domains, and impairs neuronal maturation. Mechanistically, FBXW11 associates with {beta}-catenin and alters WNT signalling. FBXW11 mutations cause the autosomal-dominant Mendelian syndrome Neurodevelopmental, Jaw, Eye and Digital syndrome (NEDJED), and we found that disease-associated variants mapped preferentially to WD40 substrate-binding repeats and {beta}-catenin contact regions, linking impaired substrate recognition to neurodevelopmental disease. Together, these findings identify FBXW11 as a conserved negative regulator of {beta}-catenin-dependent radial glial expansion and neuronal maturation during human cerebral brain development.",
  "abstract_shown": true,
  "affiliations": [
    "Dr. John and Anne Chong Lab for Functional Genomics, Charles Perkins Centre and School of Life and Environmental Sciences, The University of Sydney, Sydney, New"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "C. L. Moreno"
    },
    {
      "name": "H. King"
    },
    {
      "name": "S. Trabish"
    },
    {
      "name": "M. Thijs"
    },
    {
      "name": "D. Beck"
    },
    {
      "name": "M. Bergamasco"
    },
    {
      "name": "T. Y. D'Araujo"
    },
    {
      "name": "T. J. Mosca"
    },
    {
      "name": "R. Weatheritt"
    },
    {
      "affs": [
        0
      ],
      "name": "G. G. Neely"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/051s4sg55s39n.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.20.746070",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.20.746070v2.full",
  "id": "051s4sg55s39n",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.20.746070v2",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2806|Neurogenesis and neuroplasticity mechanisms"
    ]
  ],
  "openalex": "W7203919245",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.20.746070v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/051s4sg55s39n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:30Z",
      "native_id": "10.64898/2026.08.20.746070",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.20.746070v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "FBXW11 Activity Regulates Radial Glial Expansion in Human Cerebral Organoids",
  "title_text": "FBXW11 Activity Regulates Radial Glial Expansion in Human Cerebral Organoids",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:30Z",
  "url": "https://research.draconitic.com/paper/051s4sg55s39n",
  "venue": "bioRxiv",
  "versions": []
}