{
  "abstract": "The molecular programs that establish specialized retinal regions during development are essential for high-acuity vision, yet how their disruption contributes to human visual disorders remains poorly understood. Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), caused by pathogenic variants in NR2F1 and characterized by visual impairment, provides an opportunity to investigate these mechanisms. Using single-cell RNA sequencing of three complementary Nr2f1 mouse models, including two carrying patient-specific mutations, we identified a shared Nr2f1-dependent transcriptional program enriched in retinoic acid (RA) pathway genes. Loss or mutation of Nr2f1 disrupted the spatial organization of RA signaling, most prominently by expanding the dorso-equatorial Cyp26a1 expression domain into ventral retina and reducing ventral determinants such as Vax2. These molecular changes were associated with altered dorso-ventral distribution of S- and M-opsin-expressing cone photoreceptors. We further demonstrate that human NR2F1 binds a conserved regulatory region upstream of CYP26A1, supporting its direct role in regulating local RA availability. Finally, high-resolution optical coherence tomography in individuals with BBSOAS revealed reproducible foveal abnormalities, including a smaller and shallower foveal pit and increased central retinal thickness, consistent with foveal hypoplasia. These findings uncover a previously unrecognized retina-intrinsic component of BBSOAS visual pathology and establish an NR2F1-RA/CYP26A1 regulatory axis linking developmental retinal regionalization to human foveal specialization.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Biology Valrose (iBV) - University Cote d'Azur - Nice, France"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "P. Piovani"
    },
    {
      "name": "C. Belliardo"
    },
    {
      "name": "R. Makam"
    },
    {
      "name": "B. Zambo"
    },
    {
      "name": "A. Mantilleri"
    },
    {
      "name": "A. Chassot"
    },
    {
      "name": "G. Gogl"
    },
    {
      "name": "C. P. Schaaf"
    },
    {
      "name": "S. Blackshaw"
    },
    {
      "name": "P. Yu-Wai-Man"
    },
    {
      "name": "M. Bertacchi"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Studer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4epjmztwr05hh.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.22.753406",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753406v1.full",
  "id": "4epjmztwr05hh",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753406v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "developmental biology"
    ],
    [
      "openalex",
      "1312|Retinal Development and Disorders"
    ]
  ],
  "openalex": "W7214120875",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753406v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4epjmztwr05hh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:00Z",
      "native_id": "10.64898/2026.09.22.753406",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753406v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:developmental biology",
      "subfield": "developmental-biology"
    }
  ],
  "title": "An NR2F1-dependent retinoic acid network controls retinal specialization in mice and reveals foveal hypoplasia in patients with BBSOAS",
  "title_text": "An NR2F1-dependent retinoic acid network controls retinal specialization in mice and reveals foveal hypoplasia in patients with BBSOAS",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:00Z",
  "url": "https://research.draconitic.com/paper/4epjmztwr05hh",
  "venue": "bioRxiv",
  "versions": []
}