Homeobox protein CDX-4 explained

Homeobox protein CDX-4 is a protein that in humans is encoded by the CDX4 gene. This gene is a member of the caudal-related homeobox transcription factor family that also includes CDX1 and CDX2.[1]

Function

The transcription factor encoded by the CDX4 gene participates in the formation of extra-embryonic tissues, anterior-posterior patterning and blood formation during embryogenesis. It does so through the regulation of Hox gene expression. [2] [3] [4]

Before placentation takes place, CDX4 plays a role in its development. CDX4 mutants are born healthy and are fertile, however its importance is revealed in compound CDX mutants. Compound mutants carrying one CDX2 null allele and homozygous null for CDX4 fail to generate posterior tissue caudal to the hindlimbs and most of these embryos die around embryonic day 10.5 from lack of placental development. Around 10% of this phenotype may progress to full term, but then die shortly after birth. Upon inspection the morphogenesis of ano-rectal and urethral tissues was observed. [5] [6]

The most well described function of CDX genes are their role in caudal body formation. Transcription factors of the CDX gene family, in part control Hox gene expression by responding to signaling molecules Retinoic Acid, Wnt, and FGF. The redundant contribution of CDX4 in axial elongation is shown in that neither CDX4 null or CDX1/CDX4 compound mutants appear with impaired axial elongation. However, CDX4 does have a role in determining pancreatic B-cell number, specifying anterior-posterior location of the foregut organs including the pancreas and liver. Thus, an abnormal state is shown in embryos deficient in CDX4 by posteriorly shifted pancreas, liver and small intestines. [7] [8]

In blood formation, CDX4 regulation of Hox genes is necessary for the specification of hematopoietic cell fate during embryogenesis. This is demonstrated by the fact that blood deficiencies in CDX4 mutants can be rescued by the over expression of certain Hox genes. [9]

Knockout models have been generated in mice as described in CDX4’s role in caudal body formation.

Notes and References

  1. Web site: Entrez Gene: CDX1 caudal type homeobox transcription factor 4.
  2. van Nes J, de Graaff W, Lebrin F, Gerhard M, Beck F, Deschamps J . The Cdx4 mutation affects axial development and reveals an essential role of Cdx genes in the ontogenesis of the placental labyrinth in mice . Development . 133 . 3 . 419–28 . February 2006 . 16396910 . 10.1242/dev.02216 . free .
  3. van de Ven C, Bialecka M, Neijts R, Young T, Rowland JE, Stringer EJ, Van Rooijen C, Meijlink F, Nóvoa A, Freund JN, Mallo M, Beck F, Deschamps J . Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone . Development . 138 . 16 . 3451–62 . August 2011 . 21752936 . 10.1242/dev.066118 . free . 10400.7/644 . free .
  4. Davidson AJ, Ernst P, Wang Y, Dekens MP, Kingsley PD, Palis J, Korsmeyer SJ, Daley GQ, Zon LI . cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes . Nature . 425 . 6955 . 300–6 . September 2003 . 13679919 . 10.1038/nature01973 . 2003Natur.425..300D . 4315496 .
  5. van Nes J, de Graaff W, Lebrin F, Gerhard M, Beck F, Deschamps J . The Cdx4 mutation affects axial development and reveals an essential role of Cdx genes in the ontogenesis of the placental labyrinth in mice . Development . 133 . 3 . 419–28 . February 2006 . 16396910 . 10.1242/dev.02216 . free .
  6. van de Ven C, Bialecka M, Neijts R, Young T, Rowland JE, Stringer EJ, Van Rooijen C, Meijlink F, Nóvoa A, Freund JN, Mallo M, Beck F, Deschamps J . Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone . Development . 138 . 16 . 3451–62 . August 2011 . 21752936 . 10.1242/dev.066118 . free . 10400.7/644 . free .
  7. van de Ven C, Bialecka M, Neijts R, Young T, Rowland JE, Stringer EJ, Van Rooijen C, Meijlink F, Nóvoa A, Freund JN, Mallo M, Beck F, Deschamps J . Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone . Development . 138 . 16 . 3451–62 . August 2011 . 21752936 . 10.1242/dev.066118 . free . 10400.7/644 . free .
  8. Kinkel MD, Eames SC, Alonzo MR, Prince VE . Cdx4 is required in the endoderm to localize the pancreas and limit beta-cell number . Development . 135 . 5 . 919–29 . March 2008 . 18234725 . 10.1242/dev.010660 . free .
  9. Davidson AJ, Ernst P, Wang Y, Dekens MP, Kingsley PD, Palis J, Korsmeyer SJ, Daley GQ, Zon LI . cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes . Nature . 425 . 6955 . 300–6 . September 2003 . 13679919 . 10.1038/nature01973 . 2003Natur.425..300D . 4315496 .

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