LHX2

Lhx2, or LIM homeobox 2, is a transcription factor encoded by the LHX2 gene in vertebrates. It belongs to the LIM/homeobox gene family, which is defined by the presence of two N-terminal LIM domains and a C-terminal homeodomain that binds DNA. LHX2 forms transcriptional regulatory complexes with LIM-binding cofactors such as LDB1 and LDB2 to control the expression of target genes involved in development.

Expression of Lhx2 is prominent in neural progenitor cells of the developing forebrain, including the dorsal telencephalon, and in the developing retina, olfactory epithelium, and dorsal thalamus. Its expression patterns persist in specific neural cell populations after birth, reflecting ongoing roles in neural maintenance and differentiation.

Functions of Lhx2 include promotion of neural progenitor identity and regulation of regional forebrain patterning, notably influencing cortical hem formation and hippocampal development. In the retina, Lhx2 regulates retinal progenitor cell proliferation and the differentiation of certain neuronal cell types. Overall, Lhx2 is a key node in gene regulatory networks that balance progenitor maintenance with differentiation during neurogenesis.

Mechanistically, LHX2 operates as a transcription factor by binding DNA through its homeodomain, while the LIM domains mediate protein–protein interactions that recruit co-regulators. Through these interactions, LHX2 can activate or repress target genes in concert with other developmental regulators.

Genetic studies in mice show that loss of Lhx2 leads to severe forebrain patterning defects, including abnormalities in the hippocampus, and retinal malformations, underscoring its essential role in neural development.

Evolutionarily, LHX2 is conserved across vertebrates. In humans, LHX2 participates in neural and retinal development; while pathogenic mutations have not been widely reported, dysregulation of LHX2 signaling is studied in developmental brain and retinal disease models.