ArticleDevelopmental biology2026
An inducible system to study the regulatory functions of GSX2 in human lateral ganglionic eminence-like progenitors.
Article in Developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Animal models have demonstrated a critical role of the homeodomain transcription factor Genetic-Screened Homeobox 2 (Gsx2) in the developing basal ganglia. Moreover, recent clinical genetic studies have shown that GSX2 patient variants are associated with severe neurological symptoms and basal ganglia dysgenesis. Unfortunately, technical limitations with existing animal models, such as progenitor heterogeneity and limited temporal control, have impeded the investigation of direct regulatory targets. In this study, we engineered a Dox-inducible human embryonic stem cell (hESC) line to investigate the function of GSX2 in directed differentiation cultures that model developing lateral ganglionic eminence-like (LGE-like) progenitors. Transcriptomic, chromatin accessibility, and genomic binding studies revealed that GSX2: (1) binds both high- and low-accessibility chromatin using varying binding site preferences; (2) alters chromatin accessibility largely through indirect mechanisms; (3) functions primarily as a transcriptional repressor; and (4) regulates key conserved target genes that impact both neuronal progenitor maturation and regional specification. These results provide insight into the key regulatory roles and targets of GSX2, thereby establishing a new tractable experimental system to investigate basal ganglia development.
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