FOXG1 (Forkhead box G1) is a winged helix (forkhead) transcription factor belonging to the highly conserved FOX family of DNA binding proteins (1). In mammals, FOXG1 is expressed in the developing telencephalon (2). Expression remains detectable throughout postnatal life in specific neuronal cell populations of the hippocampus and cortex (2-4).
Functionally, FOXG1 drives the expansion of neural progenitor cells, controls the balance between proliferation, differentiation and cell cycle exit, and directs early cortical cell fate decisions, thus influencing brain size and complexity (1). In postmitotic neurons it promotes dendrite elongation, spine maintenance and synaptic plasticity, thereby influencing learning, memory, and social behavior (5).
Dosage is critical: Haploinsufficiency causes FOXG1 syndrome, characterized by microcephaly, complete agenesis of the corpus callosum, cognitive disability, dyskinesia, and epilepsy (1,2). Duplications are linked to epilepsy, movement disorders and impaired language development (2). Moreover, FOXG1 is frequently overexpressed in gliomas where it suppresses apoptosis, and its expression level correlates with tumor grade (6).
