HGNC Approved Gene Symbol: CDX4
Cytogenetic location: Xq13.2 Genomic coordinates (GRCh38): X:73,447,053-73,455,171 (from NCBI)
The CDX4 gene is a member of the 'caudal-related' family of homeobox genes (Gamer and Wright, 1993). See CDX1 (600746).
Gamer and Wright (1993) cloned a mouse Cdx4 cDNA, which encodes a predicted 282-amino acid protein. The Cdx4 homeodomain shows 82% sequence identity to the Drosophila caudal homeodomain and contains several regions of similarity to other mouse Cdx proteins. Northern blot analysis detected a single 2.4-kb transcript. In situ hybridization and immunohistochemical studies showed that the transcript is expressed during mouse embryogenesis. It is expressed transiently from 7.0 days postcoitum (dpc) to 10 dpc in neuroectoderm, presomitic and lateral plate mesoderm, and hindgut endoderm. Cdx4 exhibits a graded expression pattern with a posterior maximum, similar to that of the Drosophila caudal gene. Gamer and Wright (1993) suggested that Cdx4 has a role in the early regionalization of the embryo along the anterior-posterior axis.
Horn and Ashworth (1995) identified the human CDX4 gene which, like XIST (314670), maps to Xq13.2 within the specific region called the X-inactivation center (XIC). The Cdx4 gene in the mouse is located 100 kb distal to Xist and the 2 genes are transcribed convergently. From an analysis of a panel of YACs derived from the XIC region and flanking XIST, Horn and Ashworth (1995) demonstrated that CDX4 is located proximal to XIST in the human, indicating that both CDX4 and XIST are within the region inverted since mammalian divergence. Unlike Xist, Cdx4 appears to be normally X-inactivated in mice.
Davidson et al. (2003) identified the caudal-related gene cdx4 as the locus mutated in 'kugelig' (kgg), a zebrafish mutant with an early defect in hematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression. The blood deficiency in kgg embryos can be rescued by overexpressing the zebrafish genes hoxb7a or hoxa9a but not hoxb8a, indicating that the hematopoietic defect results from perturbations in specific hox genes. Furthermore, the hematopoietic defect in kgg mutants is not rescued by scl (187040) overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development. Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induced blood formation and altered hox gene expression. Davidson et al. (2003) concluded that taken together, their findings demonstrated that cdx4 regulates hox genes and is necessary for the specification of hematopoietic cell fate during vertebrate embryogenesis.
Davidson, A. J., Ernst, P., Wang, Y., Dekens, M. P. S., Kingsley, P. D., Palls, J., Korsmeyer, S. J., Daley, G. Q., Zon, L. I. cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes. Nature 425: 300-306, 2003. [PubMed: 13679919] [Full Text: https://doi.org/10.1038/nature01973]
Gamer, L. W., Wright, C. V. E. Murine Cdx-4 bears striking similarities to the Drosophila caudal gene in its homeodomain sequence and early expression pattern. Mech. Dev. 43: 71-81, 1993. [PubMed: 7902125] [Full Text: https://doi.org/10.1016/0925-4773(93)90024-r]
Horn, J. M., Ashworth, A. A member of the caudal family of homeobox genes maps to the X-inactivation centre region of the mouse and human X chromosomes. Hum. Molec. Genet. 4: 1041-1047, 1995. [PubMed: 7655457] [Full Text: https://doi.org/10.1093/hmg/4.6.1041]