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Xbra is a homologue of Brachyury (T) gene for Xenopus. It is a transcription activator involved in vertebrate gastrulation which controls posterior mesoderm patterning and notochord differentiation by activating transcription of genes expressed throughout mesoderm. The effects of Xbra is concentration dependent where concentration gradient controls the development of specific types of mesoderm in Xenopus. Xbra results of the expression of the FGF transcription factor, synthesized by the ventral endoderm. So while ventral mesoderm is characterized by a high concentration of FGF and Xbra, the dorsal mesoderm is characterized by a reunion of two others transcription factors, Siamois and XnR, which activates the synthesis of Goosecoid Transcription Factor. Goosecoid enables the depletion of Xbra. In a nutshell, high concentrations of Xbra induce ventral mesoderm while low concentration stimulates the formation of a back.
Posterior mesoderm development presents two types of cell behaviors, cell migration and convergent extension, in prechordal mesoderm and chordamesoderm cells, respectively. Cell migration is exhibited by the prechordal mesoderm cells, resulting in the formation of the future anterior end. Xbra induces convergent extension which inhibits cell migration and rearranges the chordamesoderm cells into a structure that will later differentiate into notochord. As a result, Xbra acts as a switch to convert between these two behaviors.
Xbra is able to activate itself indirectly, specifically for dorsal mesoderm, through FGF signaling while eFGF maintains Xbra expression, creating an autoregulatory loop.
Inhibition of Xbra leads to abnormal patterning of mesoderm, such as shortened trunk. In a previous study, the activation domain of Xbra was replaced by repressor domain of Drosophila engrailed protein in order to form a dominant-interfering Xbra construct that would help to study the function and regulation of Xbra. The injection of RNA encoding this construct has led to various birth defects such as defective blastopore closure and abnormal notochord differentiation in the developing embryo.
References
- Saka, Y; Tada, M; Smith, JC (2000). "A screen for targets of the Xenopus T-box gene Xbra". Mechanisms of Development. 93 (1–2): 27–39. doi:10.1016/S0925-4773(00)00260-4. PMID 10781937. S2CID 9583196.
- ^ Tada, M; O’Reilly, MAJ; Smith, JC (June 1997). "Analysis of competence and of Brachyury autoinduction by use of hormone-inducible Xbra". Development. 124 (11): 2225–34. doi:10.1242/dev.124.11.2225. PMID 9187148.
- ^ Kwan, Kirsten M; Kirschner, Marc W (May 1, 2003). "Xbra functions as a switch between cell migration and convergent extension in Xenopus gastrula". Development. 130 (9): 1961–1972. doi:10.1242/dev.00412. PMID 12642499. S2CID 41485337. Retrieved April 22, 2014.
- Fletcher, Russell B; Harland, Richard M (May 2008). "The Role of FGF Signaling in the Establishment and Maintenance of Mesodermal Gene Expression in Xenopus". Developmental Dynamics. 237 (5): 1243–54. doi:10.1002/dvdy.21517. PMC 3000043. PMID 18386826.
- ^ Conlon, FL; Sedgwick, SG; Weston, KM; Smith, JC (1996). "Inhibition of Xbra transcription activation causes defects in mesodermal patterning and reveals autoregulation of Xbra in dorsal mesoderm" (PDF). Development. 122 (8): 2427–35. doi:10.1242/dev.122.8.2427. PMID 8756288. Retrieved April 22, 2014.