GBX2

Homeobox protein GBX-2 is a protein that in humans is encoded by the GBX2 gene.[5][6][7]

GBX2
Identifiers
AliasesGBX2, gastrulation brain homeobox 2
External IDsOMIM: 601135 MGI: 95668 HomoloGene: 1138 GeneCards: GBX2
Gene location (Human)
Chr.Chromosome 2 (human)[1]
Band2q37.2Start236,165,236 bp[1]
End236,168,386 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
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 MbChr 1: 89.93 – 89.93 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Summary

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]

Function

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.

Animal studies

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.[9][10]

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.[11]

References

  1. GRCh38: Ensembl release 89: ENSG00000168505 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000034486 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Kowenz-Leutz E, Herr P, Niss K, Leutz A (Oct 1997). "The homeobox gene GBX2, a target of the myb oncogene, mediates autocrine growth and monocyte differentiation". Cell. 91 (2): 185–95. doi:10.1016/S0092-8674(00)80401-8. PMID 9346236. S2CID 15954797.
  6. Lin X, Swaroop A, Vaccarino FM, Murtha MT, Haas M, Ji X, Ruddle FH, Leckman JF (Feb 1996). "Characterization and sequence analysis of the human homeobox-containing gene GBX2". Genomics. 31 (3): 335–42. doi:10.1006/geno.1996.0056. PMID 8838315.
  7. "Entrez Gene: GBX2 gastrulation brain homeobox 2".
  8. Waters, S. T. “A Threshold Requirement for Gbx2 Levels in Hindbrain Development.” Development, vol. 133, no. 10, 2006, pp. 1991–2000., doi:10.1242/dev.02364.
  9. Wassarman KM, Lewandoski M, Campbell K, Joyner AL, Rubenstein JL, Martinez S, Martin GR (Aug 1997). "Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function". Development. 124 (15): 2923–34. PMID 9247335.
  10. Waters ST, Lewandoski M (May 2006). "A threshold requirement for Gbx2 levels in hindbrain development". Development. 133 (10): 1991–2000. doi:10.1242/dev.02364. PMID 16651541.
  11. Nakayama Y, Kikuta H, Kanai M, Yoshikawa K, Kawamura A, Kobayashi K, Wang Z, Khan A, Kawakami K, Yamasu K (2013). "Gbx2 functions as a transcriptional repressor to regulate the specification and morphogenesis of the mid-hindbrain junction in a dosage- and stage-dependent manner". Mechanisms of Development. 130 (11–12): 532–52. doi:10.1016/j.mod.2013.07.004. PMID 23933069.

Further reading


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