ReviewFrontiers in cell and developmental biology2026
LHX2: a transcription factor in development, homeostasis, repair, and disease.
Review in Frontiers in cell and 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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6 authors.
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Abstract
LIM homeobox 2 (LHX2) is a LIM-homeodomain (HD) transcription factor that participates in regulating vertebrate development, tissue homeostasis, and injury repair. This review systematically synthesizes the pleiotropic functions of LHX2 across multiple organ systems. During development, LHX2 directs regional specification and cell fate determination in the cerebral cortex, hippocampus, and retina, while regulating limb bud patterning and the development of the visual, olfactory, reproductive, and hematopoietic systems. During homeostasis, LHX2 acts as a key negative regulator to maintain the quiescent state of hepatic stellate cells (HSCs), osteoclast precursors, astrocytes, and hair follicle stem cells, thereby preserving tissue integrity. Following injury, LHX2 switches to a pro-regenerative mode, promoting re-epithelialization, axon regeneration, and hematopoietic niche remodeling. Dysregulation of LHX2 is causally linked to neurodevelopmental disorders, ocular malformations, liver fibrosis, osteoporosis, and various cancers. Emerging evidence also implicates LHX2 in metabolic-epigenetic circuits, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) and Wingless/Int-1 (Wnt)/β-catenin axes, as well as microRNA (miRNA) regulation. We also discuss therapeutic strategies targeting LHX2, including molecular engineering to overcome species barriers, and outline key knowledge gaps. A comprehensive understanding of LHX2-regulated networks holds promise for advancing regenerative medicine and enabling precision interventions in developmental disorders.
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