GS homeobox 1 (GSX1) is a protein encoded by the gene of the same name, located on chromosome 13 in humans [5] and chromosome 5 in mice.
GSX1 is part of the homeobox gene family and acts as a transcription factor. It is essential for the expression of growth hormone-releasing hormone (GHRH) [6] and is crucial for the development of neurons involved in sensory processing, particularly in prepulse inhibition. [7]
Additionally, GSX1 is implicated in spinal cord injury recovery, promoting neural stem cell proliferation and enhancing locomotor function in injured mice. [8]
GSX1 is a polypeptide chain consisting of 264 amino acids, with a molecular weight of 27,833 Da. [9] The GSX1 protein contains a homeodomain, a conserved protein domain that facilitates binding to double-stranded DNA, suggesting its role as a transcription 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 an activator and developmental protein. It plays a significant role in various biological processes, including transcription and transcription regulation. The protein features a DNA-binding domain and is predominantly localized in the cell nucleus, where it influences the expression of target genes. [11]
One of the key functions of GSX1 is its involvement in the expression of the growth 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 GHRH promoter, enhancing its transcriptional activity, especially in the presence of CREB-binding protein, indicating a cooperative regulatory mechanism within the hypothalamus. [6]
GSX1 plays a critical role in the development of specific neurons involved in sensory processing and cognitive regulation. Research has shown that GSX1-expressing neurons are essential for prepulse inhibition, a mechanism that helps the brain filter out irrelevant information and prevent cognitive overload. In studies using larval zebrafish and GSX1 knockout mice, the absence or silencing of these neurons resulted in significant impairments in prepulse inhibition, because they are involved in initiating startle responses. [7]
GSX1 has been implicated in tissue regeneration strategies, particularly in the context of spinal cord injury (SCI).
Promoting resident cells, especially neural stem and progenitor cells (NSPCs), is a potential approach for treating SCI. However, adult NSPCs primarily differentiate into glial cells (a type of brain cell that's not a neuron and helps support neural structure), contributing to glial scar formation at injury sites, which isn't useful. [12]
GSX1, in its developmental role, regulates the generation of excitatory and inhibitory interneurons during spinal cord embryonic development.
Recent studies show that lentivirus-mediated expression of GSX1 increases the number of NSPCs in a mouse model of SCI during shortly after injury. This expression subsequently boosts the generation of glutamatergic and cholinergic interneurons while decreasing the production interneurons that produce GABA in the long term. [8]
This ultimately means that GSX1 expression reduces reactive astrogliosis and glial scar formation, enhances serotonin neuronal activity, and improves locomotor function in injured mice, leading to better long-term outcomes. [8]
Schwann cells or neurolemmocytes are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle. The two types of Schwann cells are myelinating and nonmyelinating. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. The Schwann cell promoter is present in the downstream region of the human dystrophin gene that gives shortened transcript that are again synthesized in a tissue-specific manner.
Sonic hedgehog protein (SHH) is encoded for by the SHH gene. The protein is named after the video game character Sonic the Hedgehog.
Glial fibrillary acidic protein (GFAP) is a protein that is encoded by the GFAP gene in humans. It is a type III intermediate filament (IF) protein that is expressed by numerous cell types of the central nervous system (CNS), including astrocytes and ependymal cells during development. GFAP has also been found to be expressed in glomeruli and peritubular fibroblasts taken from rat kidneys, Leydig cells of the testis in both hamsters and humans, human keratinocytes, human osteocytes and chondrocytes and stellate cells of the pancreas and liver in rats.
Neuroregeneration is the regrowth or repair of nervous tissues, cells or cell products. Neuroregenerative mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system (PNS) and the central nervous system (CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelin sheath. The proximal segment can either die by apoptosis or undergo the chromatolytic reaction, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.
A glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.
Protein atonal homolog 1 is a protein that in humans is encoded by the ATOH1 gene.
Neurogenins, often abbreviated as Ngn, are a family of bHLH transcription factors involved in specifying neuronal differentiation. The family consisting of Neurogenin-1, Neurogenin-2, and Neurogenin-3, plays a fundamental role in specifying neural precursor cells and regulating the differentiation of neurons during embryonic development. It is one of many gene families related to the atonal gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1.
LIM homeobox transcription factor 1, alpha, also known as LMX1A, is a protein which in humans is encoded by the LMX1A gene.
Homeobox protein Nkx-2.2 is a protein that in humans is encoded by the NKX2-2 gene.
Homeobox protein EMX1 is a protein that in humans is encoded by the EMX1 gene. The transcribed EMX1 gene is a member of the EMX family of transcription factors. The EMX1 gene, along with its family members, are expressed in the developing cerebrum. EMX1 plays a role in specification of positional identity, the proliferation of neural stem cells, differentiation of layer-specific neuronal phenotypes and commitment to a neuronal or glial cell fate.
LIM homeobox 1 is a protein that in humans is encoded by the LHX1 gene. This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor important for control of differentiation and development of neural and lymphoid cells. It is also key in development of renal and urogenital systems and is required for normal organogenesis. A similar protein in mice is an essential regulator of the vertebrate head organizer.
Homeobox protein goosecoid(GSC) is a homeobox protein that is encoded in humans by the GSC gene. Like other homeobox proteins, goosecoid functions as a transcription factor involved in morphogenesis. In Xenopus, GSC is thought to play a crucial role in the phenomenon of the Spemann-Mangold organizer. Through lineage tracing and timelapse microscopy, the effects of GSC on neighboring cell fates could be observed. In an experiment that injected cells with GSC and observed the effects of uninjected cells, GSC recruited neighboring uninjected cells in the dorsal blastopore lip of the Xenopus gastrula to form a twinned dorsal axis, suggesting that the goosecoid protein plays a role in the regulation and migration of cells during gastrulation.
Chondroitin sulfate proteoglycans (CSPGs) are proteoglycans consisting of a protein core and a chondroitin sulfate side chain. They are known to be structural components of a variety of human tissues, including cartilage, and also play key roles in neural development and glial scar formation. They are known to be involved in certain cell processes, such as cell adhesion, cell growth, receptor binding, cell migration, and interaction with other extracellular matrix constituents. They are also known to interact with laminin, fibronectin, tenascin, and collagen. CSPGs are generally secreted from cells.
Homeobox protein Nkx-6.2 is a protein that in humans is encoded by the NKX6-2 gene.
Homeobox protein DBX1, also known as developing brain homeobox protein 1, is a protein that in humans is encoded by the DBX1 gene. The DBX1 gene is a transcription factor gene that is pivotal in interneuron differentiation in the ventral spinal cord.
Homeobox protein DBX2, also known as developing brain homeobox protein 2, is a protein that in humans is encoded by the DBX2 gene. DBX2, a homeodomain-containing protein, plays an important role in the development of the central nervous system, specifically in the development of the neural tube and brain. The gene DBX2 is located on chromosome 12 and is approximately 36,000 base pairs long. DBX2 is predicted to enable DNA-binding transcription activity as well as being involved in the regulation of transcription by RNA polymerase II.
Iroquois-class homeodomain protein IRX-3, also known as Iroquois homeobox protein 3, is a protein that in humans is encoded by the IRX3 gene.
Olfactory ensheathing cells (OECs), also known as olfactory ensheathing glia or olfactory ensheathing glial cells, are a type of macroglia found in the nervous system. They are also known as olfactory Schwann cells, because they ensheath the non-myelinated axons of olfactory neurons in a similar way to which Schwann cells ensheath non-myelinated peripheral neurons. They also share the property of assisting axonal regeneration.
Proneural genes encode transcription factors of the basic helix-loop-helix (bHLH) class which are responsible for the development of neuroectodermal progenitor cells. Proneural genes have multiple functions in neural development. They integrate positional information and contribute to the specification of progenitor-cell identity. From the same ectodermal cell types, neural or epidermal cells can develop based on interactions between proneural and neurogenic genes. Neurogenic genes are so called because loss of function mutants show an increase number of developed neural precursors. On the other hand, proneural genes mutants fail to develop neural precursor cells.
GS homeobox 2 (GSX2) is a protein encoded by a gene of the same name, located on chromosome 4 in humans, and on chromosome 5 in mice.