GS homeobox 2 (GSX2) is a protein encoded by a gene of the same name, located on chromosome 4 in humans, [5] and on chromosome 5 in mice. [6]
It is especially important to regulating the development of the brain, particularly during embryonic development. [7] Mutations have been linked to a variety of neurological disorders that can cause intellectual disability, dystonia (difficulty with movement) and seizures. [8]
GSX2 is a polypeptide chain consisting of 304 amino acids, with a molecular weight of 32,031. [9]
GSX2 is a homeobox transcription factor essential for mammalian forebrain development, particularly in specifying and patterning the basal ganglia. [10] [7] It binds specific DNA sequences, crucial for dorsal-ventral patterning of the telencephalon and specifying neural progenitors in the ventral forebrain. [11] [12]
GSX2 acts within a temporal framework, initially guiding the specification of striatal projection neurons during early lateral ganglionic eminence (LGE) neurogenesis, and later supporting olfactory bulb interneuron development. [13] Mutations in GSX2 have been linked to basal ganglia dysgenesis in humans, resulting in severe neurological symptoms, including dystonia and intellectual impairment. [10]
GSX2 is highly expressed in neural progenitors within the ganglionic eminences, precursors to the basal ganglia and olfactory structures. It promotes neurogenesis while inhibiting differentiation into oligodendrocytes, a type of glial cell in the central nervous system. [7]
Mutations in GSX2 have been linked to severe neurodevelopmental disorders characterized by specific brain malformations. This includes cases of basal ganglia agenesis, leading to symptoms such as a slowly progressive decline in neurologic function, dystonia, and intellectual impairment. [8]
A single nucleotide polymorphism and missense mutation in GSX2, rs1578004339, has been found to be a pathogenic cause of diencephalic-mesencephalic junction dysplasia syndrome, a neurodevelopmental disorder characterised by severe intellectual disability and seizures. [8]
