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Gastrulation Brain Homeobox 2 (Gene GBX2) Homo sapiensThe GBX2 (map locus: 2q37.2) gene product, gastrulation brain homeobox 2/Gbx2, is a 348 AA (37.3 kDa), GBX class homeoprotein transcription factor that contains a 60-AA (247-306) DNA-binding homeobox, and 8-AA polyPro (56-63), 4-AA polyAla (121-124) and 4-AA polyArg (248-251) regions. Gbx2 is expressed in all three primitive germ layers during gastrulation, Bouillet P, et al. (1995) and in pluripotent and undifferentiated stem cells making it a candidate control gene for cell pluripotency, Chapman G, et al. (1997). Gbx2 is spatially and temporally restricted in the developing central nervous system. It is expressed within the isthmic organizer (IO) at the midbrain, hindbrain border (MHB); within rhomobomeres 1-3, in the cerebellar anlage, dorsal spinal cord, dorsal thalamus, Martínez-de-la-Torre M, et al. (2002) and corpus stiatum, Bouillet P, et al. (1995). Gbx2 is overexpressed in TSU-PR1, LNCaP, PC-3, and DU145 metastatic prostate cell lines relative to the normal prostate, Gao AC and Isaacs JT, (1996) and stimulates growth of human prostate cancer cells by up-regulating interleukin-6, Gao AC, et al. (2000). Gbx2 was established as essential for the development of anterior hindbrain structures that derive from rhombomeres 1-3, Wasserman KM, et al. (1997), Li JY, et al. (2005). The development of rhombomeres (r) 1-3 origin structures depends upon different threshold levels of Gbx2, Waters ST and Lewandoski M. (2006) An important function of Gbx2 is its role in regulating neural regionalization boundaries by acting as an antagonist to Otx2. This has been most extensively studied in the development of the midbrain hindbrain boundary (MHB), the boundary between the caudal midbrain (mesencephalon) and anterior hindbrain (rhombencephalon). The expression limits of Gbx2 and Otx2 are mutually exclusive in the MHB region, wherein the posterior expression limit of Otx2 matches the anterior expression limit of Gbx2, Hidalgo-Sánchez M, et al. (1999). The MHB contains an organizing center called the isthmic organizer (IO). Otx2, Gbx2 and Fgf8 establish the position of the mid-hindbrain organizer (isthmic organizer (IO)) as reviewed by Simeone A. (2000) and Joyner AL, et al. (2000). Gbx2 helps to define the MHB organizer by antagonizing (repressing) the caudal expression of Otx2, Millet S. et al. (1999). The IO center controls anterior hindbrain and midbrain regionalization through a genetic network of genes that include Otx2, En2, Wnt1, Pax-2, Fgf8 and Gbx2, Garda AL, et al. (2001). Otx2 and Gbx2 have an overlapping expression in the isthmic region where expression of Fgf8 is induced. Fgf8 protein produced in the isthmus stabilizes and up-regulates Gbx2 expression, which, in turn, down-regulates Otx2 expression. The inductive effect of the Gbx2/Otx2 limit keeps Fgf8 expression stable and maintains its positive role in the expression of Pax2, En1,2 and Wnt1, Garda AL, et al. (2001). Otx2 and Gbx2 are required for refinement and not induction of mid-hindbrain gene expression, Li JY and Joyner AL, (2001). Otx2 and Gbx2 are required to suppress hindbrain and midbrain development, respectively. The role of Gbx2 in regulation of the midbrain hindbrain regionalization is reviewed, Hidalgo-Sánchez M, et al. (2005). Acting as an antagonist of Otx2, Gbx2 establishes the caudal (posterior) limit of the optic tectum, a midbrain structure, Katahira T, et al. (2000). The antagonist interplay of Gbx2 and Otx2 is involved in the development of inner ear structures. Gbx2 is expressed within the dorso-medial region of the otic vesicle and Otx2 is expressed in the ventral region where they help define the expression domain to induce the cochlear ganglion. Gbx2 expression is essential for the formation of the endolymphatic duct, Miyazaki H, et al. (2006), Lin Z, et al. (2005), and for macula sacculi innervation, Sánchez-Calderón H, et al. (2004). Gbx2 is involved in the development of neural crest cells and pharyngeal arch structures, Byrd NA and Meyers EN, (2005). Sigma offers antibodies and shRNAs useful for the study of GBX2 gene products. References: Bouillet P, et al. (1995) Sequence and expression pattern of the Stra7 (Gbx-2) homeobox-containing gene induced by retinoic acid in P19 embryonal carcinoma cells. Dev Dyn. 204: 372-382. |
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