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Gene Review

cdx4  -  caudal type homeo box transcription factor 4

Danio rerio

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Disease relevance of cdx4

  • The differentiation of these GABAergic markers occurs first in the first brain nerves and the cerebral ganglion and then with a several-hour delay in the caudal ganglion [1].
  • In addition, hemorrhage was observed at the caudal side of the eye [2].
  • These results demonstrate that zebrafish caudal fin regeneration is a unique model to investigate molecular mechanism(s) of TCDD toxicity [3].

High impact information on cdx4

  • Some ventralized mutants recover and develop into fertile adults, thereby revealing a requirement for chd function for the later processes of fin and caudal skeletal patterning [4].
  • The profiles were obtained from larger-scale sequencing of small RNA libraries prepared from developmentally staged zebrafish, and two adult fibroblast cell lines derived from the caudal fin (ZFL) and the liver epithelium (SJD) [5].
  • Truncate (tc) is an autosomal recessive mutation in mouse that specifically disrupts the development of the caudal notochord [6].
  • PTH2 receptor expression is greatest in the CNS, where it is concentrated in limbic, hypothalamic, and sensory areas, especially hypothalamic periventricular neurons, nerve terminals in the median eminence, superficial layers of the spinal cord dorsal horn, and the caudal part of the sensory trigeminal nucleus [7].
  • Secreted from the anterior boundary of the zebrafish neural plate, Tlc appears to protect the telencephalon from obliteration by a more caudal neural Wnt signal [8].

Biological context of cdx4


Anatomical context of cdx4

  • Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development [9].
  • Inhibiting the caudal-related genes cdx1a and cdx4 in zebrafish embryos caused ectopic expression of genes that are normally expressed in the posterior hindbrain and anterior spinal cord, and ectopic formation of the hindbrain motor and commissure neurons in the posteriormost neural tissue [12].
  • In zebrafish, mutations in cdx4 cause a severe, but not complete, deficit in embryonic blood cells [13].
  • The zebrafish gene valentino is required cell-autonomously in the development of rhombomeres 5 and 6, and valentino mutants lack visible hindbrain segmentation caudal to the r3/4 boundary (Moens, C. B., Yan, Y.-L., Appel, B., Force, A. G., and Kimmel, C. B. (1996) Development 122, 3981-3990) [14].
  • By 24 hours L3 is expressed throughout the midbrain including the region of the presumptive tectum whereas L4 is strongly expressed in the midbrain caudal to the presumptive tectum [15].

Associations of cdx4 with chemical compounds


Regulatory relationships of cdx4


Other interactions of cdx4

  • Furthermore, this method provided direct evidence for a functional role for msxb in caudal fin regeneration [25].
  • Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine [26].
  • These studies demonstrate that, in zebrafish, spi1 marks a rostral population of LPM cells committed to a myeloid fate anatomically separated from and developmentally independent of erythroid commitment in the caudal LPM [27].
  • Both wt1a and wt1b are expressed in the intermediate mesoderm, with wt1b being restricted to a smaller area lying at the caudal end of the wt1a expression domain [28].
  • We show here that vhnf1 functions in two ways to subdivide the zebrafish caudal hindbrain domain (r4-r7) into individual rhombomeres [29].

Analytical, diagnostic and therapeutic context of cdx4


  1. Development of putative GABAergic neurons in the appendicularian urochordate Oikopleura dioica. Søviknes, A.M., Chourrout, D., Glover, J.C. J. Comp. Neurol. (2005) [Pubmed]
  2. A novel smoothelin-like, actin-binding protein required for choroidal fissure closure in zebrafish. Kurita, R., Tabata, Y., Sagara, H., Arai, K., Watanabe, S. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  3. 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits zebrafish caudal fin regeneration. Zodrow, J.M., Tanguay, R.L. Toxicol. Sci. (2003) [Pubmed]
  4. Patterning the zebrafish axial skeleton requires early chordin function. Fisher, S., Halpern, M.E. Nat. Genet. (1999) [Pubmed]
  5. The developmental miRNA profiles of zebrafish as determined by small RNA cloning. Chen, P.Y., Manninga, H., Slanchev, K., Chien, M., Russo, J.J., Ju, J., Sheridan, R., John, B., Marks, D.S., Gaidatzis, D., Sander, C., Zavolan, M., Tuschl, T. Genes Dev. (2005) [Pubmed]
  6. The mouse homeobox gene Not is required for caudal notochord development and affected by the truncate mutation. Abdelkhalek, H.B., Beckers, A., Schuster-Gossler, K., Pavlova, M.N., Burkhardt, H., Lickert, H., Rossant, J., Reinhardt, R., Schalkwyk, L.C., Müller, I., Herrmann, B.G., Ceolin, M., Rivera-Pomar, R., Gossler, A. Genes Dev. (2004) [Pubmed]
  7. New members of the parathyroid hormone/parathyroid hormone receptor family: the parathyroid hormone 2 receptor and tuberoinfundibular peptide of 39 residues. Usdin, T.B., Wang, T., Hoare, S.R., Mezey, E., Palkovits, M. Frontiers in neuroendocrinology. (2000) [Pubmed]
  8. The telencephalon saved by TLC. Grove, E. Neuron (2002) [Pubmed]
  9. cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes. Davidson, A.J., Ernst, P., Wang, Y., Dekens, M.P., Kingsley, P.D., Palis, J., Korsmeyer, S.J., Daley, G.Q., Zon, L.I. Nature (2003) [Pubmed]
  10. Evolutionary constraint on Otx2 neuroectoderm enhancers-deep conservation from skate to mouse and unique divergence in teleost. Kurokawa, D., Sakurai, Y., Inoue, A., Nakayama, R., Takasaki, N., Suda, Y., Miyake, T., Amemiya, C.T., Aizawa, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Disruption of acvrl1 increases endothelial cell number in zebrafish cranial vessels. Roman, B.L., Pham, V.N., Lawson, N.D., Kulik, M., Childs, S., Lekven, A.C., Garrity, D.M., Moon, R.T., Fishman, M.C., Lechleider, R.J., Weinstein, B.M. Development (2002) [Pubmed]
  12. Cdx-Hox code controls competence for responding to Fgfs and retinoic acid in zebrafish neural tissue. Shimizu, T., Bae, Y.K., Hibi, M. Development (2006) [Pubmed]
  13. The caudal-related homeobox genes cdx1a and cdx4 act redundantly to regulate hox gene expression and the formation of putative hematopoietic stem cells during zebrafish embryogenesis. Davidson, A.J., Zon, L.I. Dev. Biol. (2006) [Pubmed]
  14. Equivalence in the genetic control of hindbrain segmentation in fish and mouse. Moens, C.B., Cordes, S.P., Giorgianni, M.W., Barsh, G.S., Kimmel, C.B. Development (1998) [Pubmed]
  15. Two Eph receptor tyrosine kinase ligands control axon growth and may be involved in the creation of the retinotectal map in the zebrafish. Brennan, C., Monschau, B., Lindberg, R., Guthrie, B., Drescher, U., Bonhoeffer, F., Holder, N. Development (1997) [Pubmed]
  16. A zebrafish retinoic acid receptor expressed in the regenerating caudal fin. White, J.A., Boffa, M.B., Jones, B., Petkovich, M. Development (1994) [Pubmed]
  17. Polycystin-2 immunolocalization and function in zebrafish. Obara, T., Mangos, S., Liu, Y., Zhao, J., Wiessner, S., Kramer-Zucker, A.G., Olale, F., Schier, A.F., Drummond, I.A. J. Am. Soc. Nephrol. (2006) [Pubmed]
  18. A unique role for 6-O sulfation modification in zebrafish vascular development. Chen, E., Stringer, S.E., Rusch, M.A., Selleck, S.B., Ekker, S.C. Dev. Biol. (2005) [Pubmed]
  19. Development of the histaminergic neurons and expression of histidine decarboxylase mRNA in the zebrafish brain in the absence of all peripheral histaminergic systems. Eriksson, K.S., Peitsaro, N., Karlstedt, K., Kaslin, J., Panula, P. Eur. J. Neurosci. (1998) [Pubmed]
  20. Organization of the olfactory system in the adult zebrafish: histological, immunohistochemical, and quantitative analysis. Byrd, C.A., Brunjes, P.C. J. Comp. Neurol. (1995) [Pubmed]
  21. Zebrafish BarH-like genes define discrete neural domains in the early embryo. Colombo, A., Reig, G., Mione, M., Concha, M.L. Gene Expr. Patterns (2006) [Pubmed]
  22. Zebrafish mdk2, a novel secreted midkine, participates in posterior neurogenesis. Winkler, C., Moon, R.T. Dev. Biol. (2001) [Pubmed]
  23. Zebrafish keratin 8 is expressed at high levels in the epidermis of regenerating caudal fin. Martorana, M.L., Tawk, M., Lapointe, T., Barre, N., Imboden, M., Joulie, C., Géraudie, J., Vriz, S. Int. J. Dev. Biol. (2001) [Pubmed]
  24. Restricted expression of the neuronal intermediate filament protein plasticin during zebrafish development. Canger, A.K., Passini, M.A., Asch, W.S., Leake, D., Zafonte, B.T., Glasgow, E., Schechter, N. J. Comp. Neurol. (1998) [Pubmed]
  25. Inhibition of zebrafish fin regeneration using in vivo electroporation of morpholinos against fgfr1 and msxb. Thummel, R., Bai, S., Sarras, M.P., Song, P., McDermott, J., Brewer, J., Perry, M., Zhang, X., Hyde, D.R., Godwin, A.R. Dev. Dyn. (2006) [Pubmed]
  26. Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine. Quint, E., Smith, A., Avaron, F., Laforest, L., Miles, J., Gaffield, W., Akimenko, M.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  27. Zebrafish SPI-1 (PU.1) marks a site of myeloid development independent of primitive erythropoiesis: implications for axial patterning. Lieschke, G.J., Oates, A.C., Paw, B.H., Thompson, M.A., Hall, N.E., Ward, A.C., Ho, R.K., Zon, L.I., Layton, J.E. Dev. Biol. (2002) [Pubmed]
  28. Identification and comparative expression analysis of a second wt1 gene in zebrafish. Bollig, F., Mehringer, R., Perner, B., Hartung, C., Schäfer, M., Schartl, M., Volff, J.N., Winkler, C., Englert, C. Dev. Dyn. (2006) [Pubmed]
  29. vhnf1 and Fgf signals synergize to specify rhombomere identity in the zebrafish hindbrain. Wiellette, E.L., Sive, H. Development (2003) [Pubmed]
  30. Analysis of thrombocyte development in CD41-GFP transgenic zebrafish. Lin, H.F., Traver, D., Zhu, H., Dooley, K., Paw, B.H., Zon, L.I., Handin, R.I. Blood (2005) [Pubmed]
  31. Sequence and expression of glutamic acid decarboxylase isoforms in the developing zebrafish. Martin, S.C., Heinrich, G., Sandell, J.H. J. Comp. Neurol. (1998) [Pubmed]
  32. Gdf5 is expressed in the developing skeleton of median fins of late-stage zebrafish, Danio rerio. Crotwell, P.L., Clark, T.G., Mabee, P.M. Dev. Genes Evol. (2001) [Pubmed]
  33. Functional evidence for visuospatial coding in the Mauthner neuron. Canfield, J.G. Brain Behav. Evol. (2006) [Pubmed]
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