Contents

GBX2

Protein-coding gene in the species Homo sapiens

GBX2
Identifiers
Aliases	GBX2, gastrulation brain homeobox 2
External IDs	OMIM: 601135; MGI: 95668; HomoloGene: 1138; GeneCards: GBX2; OMA:GBX2 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q37.2 Start 236,165,236 bp[1] End 236,168,386 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 D|1 45.06 cM Start 89,855,678 bp[2] End 89,858,901 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gonad testicle putamen stromal cell of endometrium caudate nucleus C1 segment hypothalamus nucleus accumbens substantia nigra right hemisphere of cerebellum Top expressed in zygote primary oocyte medial dorsal nucleus tail of embryo primitive streak secondary oocyte medial geniculate nucleus otic vesicle embryo lumbar subsegment of spinal cord More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription factor activity RNA polymerase II core promoter sequence-specific DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific transcription factor binding Cellular component nucleus Biological process autonomic nervous system development midbrain-hindbrain boundary morphogenesis regulation of transcription, DNA-templated thalamus development hindbrain development transcription by RNA polymerase II tube morphogenesis transcription, DNA-templated nervous system development cerebellum development cerebellar granule cell precursor proliferation axon guidance forebrain neuron development midbrain-hindbrain boundary development rhombomere 2 development inner ear morphogenesis neural crest cell migration branching involved in blood vessel morphogenesis cell population proliferation positive regulation of transcription by RNA polymerase II regulation of nervous system development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2637 14472 Ensembl ENSG00000168505 ENSMUSG00000034486 UniProt P52951 P48031 RefSeq (mRNA) NM_001485 NM_001301687 NM_010262 RefSeq (protein) NP_001288616 NP_001476 NP_034392 Location (UCSC) Chr 2: 236.17 – 236.17 Mb Chr 1: 89.86 – 89.86 Mb PubMed search [3] [4]
Wikidata
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Homeobox protein GBX-2 is a protein that in humans is encoded by the GBX2 gene.^[5][6][7]

Gastrulation Brain Homeobox 2, or commonly known as GBX2, is a type of transcription factor that aids in the arranging of the midbrain and hindbrain during gastrulation. The hindbrain is broken up into seven or eight rhombomeres during gastrulation and GBX2 is responsible for rhombomeres one through three. GBX2 also takes part in the signaling and expression of other genes. It has been said that there is a threshold requirement for the amount of GBX2, so what occurs depends on the amount expressed. For example, specific amounts of GBX2 is needed for regulating the anterior and posterior patterning in the hindbrain. If the specific threshold is not met, then the patterning does not occur. This is the case with the other genes it helps to express like FGF8. With every gene comes some diseases associated with it. Colon Small Cell Carcinoma and Optiz-Gbbb Syndrome, which causes abnormalities throughout the midline of the body, are the diseases most closely associated with the GBX2 gene. ^[8]

Gastrulation Brain Homeobox 2 (GBX2) is a homeobox gene involved in the normal development of rhombomeres 1-3 which is the mid/hindbrain region. This gene is a dosage dependent transcription factor involved in the regulation of proper expression of other genes. GBX2 expression occurs during gastrulation and continues to be expressed in the later stages of embryogenesis. During these different stages, GBX2 is responsible for several important processes. In the neural plate stage GBX2 is required in order for the anterior hindbrain precursors to survive and form correctly. Also at this stage in development GBX2 is required for the proper regulation of different gene expression needed for the early establishment of A/P patterning in the neural plate. In the early stages of brain morphogenesis GBX2 is required for both the normal development of the anterior hindbrain and the proper formation of the mid/hindbrain organizer. Because of the effects on the mid/hindbrain organizer, GBX2 is involved in the positioning of the expression domain for isthmic FGF8. Since this is a dosage dependent gene, the different amounts of gene present in certain location can cause different outcomes. FGF8 is affected by the different dosages in the location it is expressed. The absence of GBX2 causes FGF8 expression is shifted caudally and over expression of GBX2 causes FGF8 expression to be shifted rostrally. Not all of the rhombomeres GBX2 is expressed in require the same strictness of dose regulation. Of the three, rhombomere 2 has the most strict dose requirements.

The Gbx-2 gene is thought to be involved in neural crest cell patterning and differentiation during fetal growth as a transcription factor. As a zygote becomes a gastrula, the embryonic ectoderm differentiates into these neural crest cells, which give rise to many structures including muscle, neurons, and bone later in development. In order to test Gbx-2's role in neural crest cell development, the region of neural cell proliferation was injected with the morphogen Wnt8. In response, Snail2 was expressed, which led to transcription factor activation and subsequent protein formation. When Wnt8 was inhibited in the same region, no transcription factors were expressed and neural cell growth was inhibited or not seen. There have also been studies that showed that when the reverse occurred, with the absence or presence of Snail2 affecting Wnt8, similar effects to transcription factor activation occurred. Such research has shown that transcription factor activation is dependent on both genes. Wnt is thought to be a neural crest cell inducer, and Gbx-2 is one of the gene targets involved.^[9] In cases where Gbx-2 mRNA is in excess, an expansion of neural crest cells is seen, whereas when there is a lack of mRNA, neural crest cells fail to proliferate. If neural crest cells are unable to proliferate, many of the body's important organs and processes will be inhibited and could likely lead to miscarriage of the fetus.

Knockout of the GBX2 gene causes the failure of many structures to form, such as the isthmic nuclei, the cerebellum, motor nerve V and many other derivatives of rhombomeres 1-3. GBX2 gene knockout embryos will continue to develop and will reach full term pregnancy. The babies are born but if there is a lack of GBX2 expression all will die soon after birth.^[10][11]

Knockdown of the gbx2 gene leads to a truncated anterior hindbrain as well as abnormal clusters of cell bodies in r2 and r3 which are associated with problems in cranial nerve V. It has been shown that any structures derived from r1-r3 will be adversely affected by mutations or deficiencies in gbx2. These structures include the aortic arch and right Subclavian artery which, when improperly developed, can lead to cardiovascular defects in addition to craniofacial defects from improper development of cranial nerve V.^[12]

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