GSX2
This article will address the topic of GSX2, which is of great relevance and topicality in the _var2 field. Its impact on society will be analyzed, as well as its implications on _var3. In addition, different perspectives and approaches related to GSX2 will be considered, with the aim of providing a comprehensive and complete vision on this topic. By reviewing updated and contrasted information, the aim is to offer the reader a clear and objective vision of GSX2, as well as the possible consequences that its development may generate in the future.
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]
Structure
GSX2 is a polypeptide chain consisting of 304 amino acids, with a molecular weight of 32,031.[9]
Function
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]
Clinical significance
Neurodevelopmental disorders
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]
Diencephalic-mesencephalic junction dysplasia syndrome
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]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000180613 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000035946 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Gene symbol report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2024-10-23.
- ^ "GSX2 Gene Detail". Mouse Genome Informatics. Retrieved 23 October 2024.
- ^ a b c De Mori R, Severino M, Mancardi MM, Anello D, Tardivo S, Biagini T, et al. (October 2019). "Agenesis of the putamen and globus pallidus caused by recessive mutations in the homeobox gene GSX2". Brain. 142 (10): 2965–2978. doi:10.1093/brain/awz247. PMC 6776115. PMID 31412107.
- ^ a b c "VCV000694062.3 - ClinVar - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2024-10-24.
- ^ "UniProt". www.uniprot.org. Retrieved 2024-10-23.
- ^ a b Gebelein B. "Gsx Factors and Impacts on Development and Disease". Gebelein Lab. Cincinnati Children's Hospital.
- ^ Méndez-Gómez HR, Vicario-Abejón C (2012). "The homeobox gene Gsx2 regulates the self-renewal and differentiation of neural stem cells and the cell fate of postnatal progenitors". PLOS ONE. 7 (1) e29799. Bibcode:2012PLoSO...729799M. doi:10.1371/journal.pone.0029799. PMC 3252334. PMID 22242181.
- ^ Webb JA, Farrow E, Cain B, Yuan Z, Yarawsky AE, Schoch E, et al. (July 2024). "Cooperative Gsx2-DNA binding requires DNA bending and a novel Gsx2 homeodomain interface". Nucleic Acids Research. 52 (13): 7987–8002. doi:10.1093/nar/gkae578. PMC 11260444. PMID 38932680.
- ^ Waclaw RR, Wang B, Pei Z, Ehrman LA, Campbell K (August 2009). "Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates". Neuron. 63 (4): 451–465. doi:10.1016/j.neuron.2009.07.015. PMC 2772064. PMID 19709628.