GS homeobox 1 (GSX1) is aprotein encoded by the gene of the same name, located onchromosome 13 in humans[5] and chromosome 5 inmice.
GSX1 is part of thehomeobox gene family and acts as a transcription factor. It is essential for the expression ofgrowth hormone-releasing hormone (GHRH)[6] and is crucial for the development ofneurons involved insensory processing, particularly inprepulse inhibition.[7]
Additionally, GSX1 is implicated inspinal cord injury recovery, promoting neuralstem cell proliferation and enhancinglocomotor function in injuredmice.[8]
GSX1 is apolypeptide chain consisting of 264amino acids, with amolecular weight of 27,833 Da.[9] The GSX1 protein contains ahomeodomain, a conserved protein domain that facilitates binding to double-stranded DNA, suggesting its role as atranscription factor.[10]
The GSX1 gene is located on the short arm of chromosome 13 at the cytogenetic band 13q12.3. It is part of a larger family of homeobox genes, which are crucial for developmental processes and the regulation of gene expression during embryonic development.[5]
GSX1 is classified as anactivator and developmental protein. It plays a significant role in various biological processes, includingtranscription andtranscription regulation. The protein features aDNA-binding domain and is predominantly localized in thecell nucleus, where it influences the expression of target genes.[11]
One of the key functions of GSX1 is its involvement in the expression of thegrowth hormone-releasing hormone (GHRH) gene. Research indicates that GSX1, known as Gsh-1 in mice, is essential for GHRH gene expression.
A study demonstrated that the absence of Gsh-1 in knockout mice resulted in a dwarf phenotype and a complete loss of GHRH expression. This study elucidated that GSX1 binds to multiple regulatory sites in the GHRHpromoter, enhancing its transcriptional activity, especially in the presence ofCREB-binding protein, indicating a cooperative regulatory mechanism within thehypothalamus.[6]
GSX1 plays a critical role in the development of specificneurons involved insensory processing and cognitive regulation. Research has shown that GSX1-expressingneurons are essential forprepulse inhibition, a mechanism that helps the brain filter out irrelevant information and prevent cognitive overload. In studies using larvalzebrafish and GSX1 knockoutmice, the absence or silencing of theseneurons resulted in significant impairments inprepulse inhibition, because they are involved in initiatingstartle responses.[7]
GSX1 has been implicated in tissue regeneration strategies, particularly in the context ofspinal cord injury (SCI).
Promoting resident cells, especiallyneural stem andprogenitor cells (NSPCs), is a potential approach for treating SCI. However, adult NSPCs primarily differentiate intoglial cells (a type of brain cell that's not aneuron and helps support neural structure), contributing toglial scar formation at injury sites, which isn't useful.[12]
GSX1, in its developmental role, regulates the generation of excitatory and inhibitoryinterneurons during spinal cordembryonic development.
Recent studies show thatlentivirus-mediated expression of GSX1 increases the number of NSPCs in amouse model of SCI during shortly after injury. This expression subsequently boosts the generation of glutamatergic and cholinergicinterneurons while decreasing the productioninterneurons that produceGABA in the long term.[8]
This ultimately means that GSX1 expression reduces reactiveastrogliosis andglial scar formation, enhancesserotonin neuronal activity, and improves locomotor function in injuredmice, leading to better long-term outcomes.[8]
