Cdx

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The Cdx gene family, also called caudal genes, are a group of genes found in many animal genomes. Cdx genes contain a homeobox DNA sequence and code for proteins that act as transcription factors. The gene after which the gene family is named (the founding member) is the caudal or cad gene of the fruitfly Drosophila melanogaster. [1] [2] The human genome has three Cdx genes, called CDX1 , CDX2 and CDX4 . The zebrafish has no cdx2 gene, but two copies of cdx1 and one copy of cdx4. [3] The Cdx gene in the nematode Caenorhabditis elegans is called pal-1. [4]

The Cdx gene family has been suggested to regulate early mesoderm cell fate decisions The gene’s function has been found to impact both hematopoiesis of the yolk sac and cardiogenesis in zebrafish. Cdx2 specifically is the gene responsible for normal expression of certain cardiogenic transcription factors which regulate cardiac and blood development during embryogenesis. Cdx has been suggested to function with the mesoderm to direct fate decisions of cells through transcription regulation. This suggests that the Cdx gene influences target gene expression through epigenetic control. [5]

Cdx genes play many roles during embryological development. This is particularly seen during the development of the body plan. Cdx genes are transcription factors that are influenced by signaling molecules such as Wnt, Retinoic acid and FGF (fibroblast growth factor) during body plan establishment in the developing embryo. [6] Expression of Cdx is responsible for the control of the Hox gene family, which establishes the body plan posteriorly and anteriorly. The timed release of signaling molecules establishes the anterior/posterior axis formation and facilitates the regression of the primitive node. Hox genes area also critical for the proper orientation of the head, legs, arms, thorax and abdomen. Transfer of this information to Hox genes for positional development works directly through Cdx binding sites. Mutations to these binding sites have shown to ultimately prevent Hox gene expression and affect proper establishment of the body plan by preventing regulation of region-specific expression. [7]

Research demonstrating decreases in Cdx dosage within mice has shown defects in anterior and posterior axis development. This has shown more severe vertebral defects posteriorly as Cdx dosage decreases. Along with this, it has been found that as Cdx dosage decreases, modification of Wnt signaling, and timing of Hox expression causes both neurological and skeletal defects in the posterior vertebra. [8]

Cdx1, Cdx2, and Cdx4 each have individual roles as well as overlapping roles where, if one gene has been knocked out, the others would be able to compensate to some degree to make up for a single gene deficiency. The Cdx genes function more separately in the development of the gut where the knockout of one gene would have a larger impact on the overall development of the embryo. Knockout of the Cdx1 gene would result in a posterior structure such as a rip, developing the morphology of a more anterior rib, but would not result in any gut abnormalities. Knockout of the Cdx2 gene however would result in the same axial homeotic shift and knocking out the Cdx1 gene, but could also prevent trophoblast maturation and blastocyst implantation if the knockout was in both alleles. Cdx2 gene knockout would also result in multiple polyps in the midgut which are related to cancer cells. The function of Cdx4 in gut development is currently unknown since no spontaneous mutations have been observed nor have any knockout experiments been performed. [9]

Related Research Articles

<span class="mw-page-title-main">Homeobox</span> DNA pattern affecting anatomy development

A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of the full-grown organism.

The ParaHox gene cluster is an array of homeobox genes from the Gsx, Xlox (Pdx) and Cdx gene families.

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment, and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves.

<span class="mw-page-title-main">Apical ectodermal ridge</span>

The apical ectodermal ridge (AER) is a structure that forms from the ectodermal cells at the distal end of each limb bud and acts as a major signaling center to ensure proper development of a limb. After the limb bud induces AER formation, the AER and limb mesenchyme—including the zone of polarizing activity (ZPA)—continue to communicate with each other to direct further limb development.

The limb bud is a structure formed early in vertebrate limb development. As a result of interactions between the ectoderm and underlying mesoderm, formation occurs roughly around the fourth week of development. In the development of the human embryo the upper limb bud appears in the third week and the lower limb bud appears four days later.

In the field of developmental biology, regional differentiation is the process by which different areas are identified in the development of the early embryo. The process by which the cells become specified differs between organisms.

<span class="mw-page-title-main">CDX2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein CDX-2 is a protein that in humans is encoded by the CDX2 gene. The CDX2 protein is a homeobox transcription factor expressed in the nuclei of intestinal epithelial cells, playing an essential role in the development and function of the digestive system. CDX2 is part of the ParaHox gene cluster, a group of three highly conserved developmental genes present in most vertebrate species. Together with CDX1 and CDX4, CDX2 is one of three caudal-related genes in the human genome.

<span class="mw-page-title-main">HOXB7</span> Protein-coding gene in humans

Homeobox protein Hox-B7 is a protein that in humans is encoded by the HOXB7 gene.

<span class="mw-page-title-main">PITX2</span> Protein-coding gene in the species Homo sapiens

Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.

<span class="mw-page-title-main">HOXB6</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-B6 is a protein that in humans is encoded by the HOXB6 gene.

<span class="mw-page-title-main">Homeobox A1</span> Protein-coding gene in humans

Homeobox protein Hox-A1 is a protein that in humans is encoded by the HOXA1 gene.

<span class="mw-page-title-main">HOXA3</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-A3 is a protein that in humans is encoded by the HOXA3 gene.

<span class="mw-page-title-main">CDX1</span> Protein-coding gene in the species Homo sapiens

Homeobox protein CDX-1 is a protein in humans that is encoded by the CDX1 gene. CDX1 is expressed in the developing endoderm and its expression persists in the intestine throughout adulthood. CDX1 protein expression varies along the intestine, with high expression in intestinal crypts and diminishing expression along intestinal villi.

<span class="mw-page-title-main">GBX2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein GBX-2 is a protein that in humans is encoded by the GBX2 gene.

<span class="mw-page-title-main">Zone of polarizing activity</span>

The zone of polarizing activity (ZPA) is an area of mesenchyme that contains signals which instruct the developing limb bud to form along the anterior/posterior axis. Limb bud is undifferentiated mesenchyme enclosed by an ectoderm covering. Eventually, the limb bud develops into bones, tendons, muscles and joints. Limb bud development relies not only on the ZPA, but also many different genes, signals, and a unique region of ectoderm called the apical ectodermal ridge (AER). Research by Saunders and Gasseling in 1948 identified the AER and its subsequent involvement in proximal distal outgrowth. Twenty years later, the same group did transplantation studies in chick limb bud and identified the ZPA. It wasn't until 1993 that Todt and Fallon showed that the AER and ZPA are dependent on each other.

Homeotic genes are genes which regulate the development of anatomical structures in various organisms such as echinoderms, insects, mammals, and plants. Homeotic genes often encode transcription factor proteins, and these proteins affect development by regulating downstream gene networks involved in body patterning.

The Cdx protein family is a group of the transcription factor proteins which bind to DNA to regulate the expression of genes. In particular this family of proteins can regulate the Hox genes. They are regulators of embryonic development and hematopoiesis in vertebrates, and are also involved in the development of some types of gastrointestinal cancers and leukemias.

tinman, or tin is an Nk2-homeobox containing transcription factor first isolated in Drosophila flies. The human homolog is the Nkx2-5 gene. tinman is expressed in the precardiac mesoderm and is responsible for the differentiation, proliferation, and specification of cardiac progenitor cells. This gene is named after the character Tin Woodman who lacks a heart, as flies with nonfunctional tinman genes have cardiac deformities.

<span class="mw-page-title-main">Hox genes in amphibians and reptiles</span>

Hox genes play a massive role in some amphibians and reptiles in their ability to regenerate lost limbs, especially HoxA and HoxD genes.

<span class="mw-page-title-main">CDX4 (gene)</span> Protein-coding gene in humans

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.

References

  1. ↑ Mlodzik, Marek; Fjose, Anders; Gehring, Walter J. (1985). "Isolation of caudal, a Drosophila homeo box-containing gene with maternal expression, whose transcripts form a concentration gradient at the pre-blastoderm stage". The EMBO Journal. 4 (11): 2961–9. doi:10.1002/j.1460-2075.1985.tb04030.x. PMC   554605 . PMID   16453641.
  2. ↑ "FlyBase cad gene" . Retrieved 7 December 2012.
  3. ↑ Mulley, John F.; Chiu, Chi-hua; Holland, Peter W. H. (2006). "Breakup of a homeobox cluster after genome duplication in teleosts". Proceedings of the National Academy of Sciences. 103 (27): 10369–72. Bibcode:2006PNAS..10310369M. doi: 10.1073/pnas.0600341103 . JSTOR   30049630. PMC   1502464 . PMID   16801555.
  4. ↑ Holland, Peter W. H.; Brooke, Nina M.; Garcia-Fernàndez, Jordi (1998). "The Para Hox gene cluster is an evolutionary sister of the Hox gene cluster". Nature. 392 (6679): 920–2. Bibcode:1998Natur.392..920B. doi:10.1038/31933. PMID   9582071. S2CID   4398740.
  5. ↑ Foley, TE; Hess, B; Savory, JGA; Ringuette, R; Lohnes, D (1 April 2019). "Role of Cdx factors in early mesodermal fate decisions". Development. 146 (7): dev170498. doi: 10.1242/dev.170498 . PMID   30936115.
  6. ↑ Neijts, Roel; Amin, Shilu; Van Rooijen, Carina; Deschamps, Jacqueline (2017). "Cdx is crucial for the timing mechanism driving colinear Hox activation and defines a trunk segment in the Hox cluster topology". Developmental Biology. 422 (2): 146–154. doi: 10.1016/j.ydbio.2016.12.024 . PMID   28041967.
  7. ↑ Charité, Jeroen; de Graaff, Wim; Consten, Dimitri; Reijnen, Mark J.; Korving, Jeroen; Deschamps, J (1998). "Transducing positional information to the Hox genes: Critical interaction of cdx gene products with position-sensitive regulatory elements". Development. 125 (22): 4349–58. doi:10.1242/dev.125.22.4349. PMID   9778495. S2CID   44221462.
  8. ↑ Van De Ven, Cesca; Bialecka, Monika; Neijts, Roel; Young, Teddy; Rowland, Jennifer E.; Stringer, Emma J.; Van Rooijen, Carina; Meijlink, Frits; Nóvoa, Ana; Freund, Jean-Noel; Mallo, Moises; Beck, Felix; Deschamps, Jacqueline (2011). "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. doi: 10.1242/dev.066118 . hdl: 10400.7/644 . PMID   21752936.
  9. ↑ Beck, F (October 2004). "The role of Cdx genes in the mammalian gut". Gut. 53 (10): 1394–1396. doi: 10.1136/gut.2003.038240 . PMC   1774238 . PMID   15361482.
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