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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.

Original publication

DOI

10.1126/sciadv.adt5859

Type

Journal article

Journal

Sci Adv

Publication Date

05/09/2025

Volume

11

Keywords

Humans, Cell Polarity, Galectin 3, Animals, Human Embryonic Stem Cells, Neurogenesis, Mice, Gene Expression Regulation, Developmental, Cell Differentiation, Female, Neural Stem Cells