Galectin-3 induces neurodevelopmental apical-basal polarity and regulates gyrification
Apical-basal polarity (ABP) establishment and maintenance is necessary for proper brain development, yet how it is controlled is unclear. Galectin-3 (Gal-3) has been previously implicated in ABP of epithelial cells, and, here, we find that it is apically expressed in human embryonic stem cells (hESCs) during neural induction. Gal-3 blockade disrupts ABP and alters the distribution of junctional proteins in hESC-derived neural rosettes and is rescued by addition of recombinant Gal-3. Transcriptomics analysis shows that blocking Gal-3 regulates expression of genes responsible for nervous system development and cell junction assembly, among others. Last, Gal-3 blockade during embryonic development in vivo reduces horizontal cell divisions, disturbs cortical layering of neural progenitors, and induces gyrification. These data uncover a regulatory mechanism for ABP in the brain and warrant caution in modulating Gal-3 during pregnancy.
Authors
- Zoltán Molnár (ORCID: https://orcid.org/0000-0002-6852-6004)
- Ning Huang (ORCID: https://orcid.org/0000-0001-8874-3439)
- Luana Campos Soares (ORCID: https://orcid.org/0000-0001-9127-7061)
- Francis G. Szele (ORCID: https://orcid.org/0000-0002-2931-0673)
- James Hillis (ORCID: https://orcid.org/0000-0003-0435-0879)
- Elisa M. Cruz (ORCID: https://orcid.org/0000-0002-5861-3729)
- Sara Bandiera (ORCID: https://orcid.org/0000-0002-1203-8554)
- Yan Dai (ORCID: https://orcid.org/0000-0001-5890-8087)
- Eric O’Neill (ORCID: https://orcid.org/0000-0002-0060-6278)
- Mootaz M. Salman (ORCID: https://orcid.org/0000-0002-5683-1706)
- Dhanu Gupta (ORCID: https://orcid.org/0000-0003-0163-2678)
- Lara Nikel (ORCID: https://orcid.org/0000-0002-1577-2105)
- Matthew J. A. Wood (ORCID: https://orcid.org/0000-0002-5436-6011)
- Viviana Macarelli (ORCID: https://orcid.org/0000-0002-5875-8290)
- Marva Chan (ORCID: https://orcid.org/0000-0001-8604-4300)
- Talia Vasaturo-Kolodner
- Hana Bernhardova (ORCID: https://orcid.org/0009-0003-1797-9374)
Institutions
- Harvard University (US)
- Dalian Medical University (CN)
- Karolinska Institutet (SE)
- Yale University (US)
- University of Oxford (GB)
- Massachusetts General Hospital (US)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Dementia UK (GB)
- UK Dementia Research Institute (GB)
- Oxford BioMedica (United Kingdom) (GB)
- Chongqing Medical University (CN)
- Stanford University (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-09-03
- DOI
- https://doi.org/10.1126/sciadv.adt5859
- Citations
- 1
- Primary Topic
- Galectins and Cancer Biology
- Type
- article
- Field-Weighted Citation Impact
- 0.80