Gene Symbol: hoxd4a
Description: homeobox D4a
Alias: etID309823.9, etID37000.9, fb36c05, hoxd4, wu:fb36c05, homeobox protein Hox-D4a, homeo box D4a, homeobox gene D-4, hox-D4
Species: zebrafish
Products:     hoxd4a

Top Publications

  1. Gongal P, Waskiewicz A. Zebrafish model of holoprosencephaly demonstrates a key role for TGIF in regulating retinoic acid metabolism. Hum Mol Genet. 2008;17:525-38 pubmed
    ..The consequences of abnormal RA levels for forebrain patterning are profound, and imply that in human patients with TGIF deficiencies, increased forebrain RA levels contribute to the development of HPE. ..
  2. Maves L, Kimmel C. Dynamic and sequential patterning of the zebrafish posterior hindbrain by retinoic acid. Dev Biol. 2005;285:593-605 pubmed
    ..We show that early zebrafish rhombomere-specification genes, including vhnf1 in r5-r6 and hoxd4a in r7, initiate expression sequentially in the hindbrain, each adjacent to the source of RA synthesis in paraxial ..
  3. Hernandez R, Putzke A, Myers J, Margaretha L, Moens C. Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development. Development. 2007;134:177-87 pubmed
    ..We present a ;gradient-free' model for hindbrain patterning in which differential RA responsiveness along the hindbrain anterior-posterior axis is shaped primarily by the dynamic expression of RA-degrading enzymes. ..
  4. Zannino D, SAGERSTROM C, Appel B. olig2-Expressing hindbrain cells are required for migrating facial motor neurons. Dev Dyn. 2012;241:315-26 pubmed publisher
    ..Our data raise the possibility that cells expressing olig2 are intermediate targets that help guide facial motor neuron migration. ..
  5. Gongal P, March L, Holly V, Pillay L, Berry Wynne K, Kagechika H, et al. Hmx4 regulates Sonic hedgehog signaling through control of retinoic acid synthesis during forebrain patterning. Dev Biol. 2011;355:55-64 pubmed publisher
    ..We propose that Hmx4 is a critical regulator of retinoic acid synthesis in a developing embryo, and that this regulation is essential for controlling Shh signaling and forebrain development. ..
  6. Dong X, Li J, He L, Gu C, Jia W, Yue Y, et al. Zebrafish Znfl1 proteins control the expression of hoxb1b gene in the posterior neuroectoderm by acting upstream of pou5f3 and sall4 genes. J Biol Chem. 2017;292:13045-13055 pubmed publisher
  7. Linville A, Radtke K, Waxman J, Yelon D, Schilling T. Combinatorial roles for zebrafish retinoic acid receptors in the hindbrain, limbs and pharyngeal arches. Dev Biol. 2009;325:60-70 pubmed publisher
    ..These studies reveal novel tissue-specific roles for RARs in controlling the competence and sensitivity of cells to respond to RA. ..
  8. Skromne I, Thorsen D, Hale M, Prince V, Ho R. Repression of the hindbrain developmental program by Cdx factors is required for the specification of the vertebrate spinal cord. Development. 2007;134:2147-58 pubmed
    ..We propose that by preventing the posterior-most region of the neural plate from following a hindbrain developmental program, Cdx factors help determine the size of the prospective hindbrain and spinal cord territories. ..
  9. Plessy C, Dickmeis T, Chalmel F, Strahle U. Enhancer sequence conservation between vertebrates is favoured in developmental regulator genes. Trends Genet. 2005;21:207-10 pubmed

More Information


  1. Wang J, Préfontaine G, Lemieux M, Pope L, Akimenko M, Hache R. Developmental effects of ectopic expression of the glucocorticoid receptor DNA binding domain are alleviated by an amino acid substitution that interferes with homeodomain binding. Mol Cell Biol. 1999;19:7106-22 pubmed
    ..These results highlight the potential of DNA-independent effects of GR in a whole-animal model and suggest that at least some of these effects may result from direct interactions with homeodomain proteins. ..
  2. Henshall T, Tucker B, Lumsden A, Nornes S, Lardelli M, Richards R. Selective neuronal requirement for huntingtin in the developing zebrafish. Hum Mol Genet. 2009;18:4830-42 pubmed publisher
    ..These investigations demonstrate a specific 'rate-limiting' role for huntingtin in formation of the telencephalon and the pre-placodal region, and differing levels of requirement for huntingtin function in specific nerve cell types. ..
  3. Shimozono S, Iimura T, Kitaguchi T, Higashijima S, Miyawaki A. Visualization of an endogenous retinoic acid gradient across embryonic development. Nature. 2013;496:363-6 pubmed publisher
  4. Love C, Prince V. Expression and retinoic acid regulation of the zebrafish nr2f orphan nuclear receptor genes. Dev Dyn. 2012;241:1603-15 pubmed publisher
    ..Our finding that RA positively regulates nr2f1a expression in the trunk supports the possibility that Nr2fs function in a negative feedback loop to modulate RA signaling in this region. ..
  5. Breau M, Wilkinson D, Xu Q. A Hox gene controls lateral line cell migration by regulating chemokine receptor expression downstream of Wnt signaling. Proc Natl Acad Sci U S A. 2013;110:16892-7 pubmed publisher
  6. Mehta T, Ravi V, Yamasaki S, Lee A, Lian M, Tay B, et al. Evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum). Proc Natl Acad Sci U S A. 2013;110:16044-9 pubmed publisher
    ..Such a relationship suggests that the first two rounds of genome duplication may have occurred independently in the lamprey and gnathostome lineages. ..
  7. Mungpakdee S, Seo H, Chourrout D. Spatio-temporal expression patterns of anterior Hox genes in Atlantic salmon (Salmo salar). Gene Expr Patterns. 2008;8:508-14 pubmed publisher
    ..However, changes in spatial expression were observed for the ancient fish gene duplicate HoxB3b, while recently duplicated genes showed divergence in their expression levels. ..
  8. Amores A, Suzuki T, Yan Y, Pomeroy J, Singer A, Amemiya C, et al. Developmental roles of pufferfish Hox clusters and genome evolution in ray-fin fish. Genome Res. 2004;14:1-10 pubmed
  9. Drummond D, Cheng C, Selland L, Hocking J, Prichard L, Waskiewicz A. The role of Zic transcription factors in regulating hindbrain retinoic acid signaling. BMC Dev Biol. 2013;13:31 pubmed publisher
    ..Zic transcription factors function in patterning hindbrain motor neurons through their regulation of embryonic retinoic acid signaling. ..
  10. Nolte C, Rastegar M, Amores A, Bouchard M, Grote D, Maas R, et al. Stereospecificity and PAX6 function direct Hoxd4 neural enhancer activity along the antero-posterior axis. Dev Biol. 2006;299:582-93 pubmed
    ..embryos having decreased pax6a and/or pax6b activity display malformed rhombomere boundaries and an anteriorized hoxd4a expression border...
  11. Moghadam H, Ferguson M, Danzmann R. Evolution of Hox clusters in Salmonidae: a comparative analysis between Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). J Mol Evol. 2005;61:636-49 pubmed
    ..However, our data suggest that phylogenetically, the homologous genes within each cluster express mosaic relationships among the teleosts tested and, thus, leave unresolved the interfamilial relationships among these taxa. ..
  12. Nolte C, Amores A, Nagy Kovács E, Postlethwait J, Featherstone M. The role of a retinoic acid response element in establishing the anterior neural expression border of Hoxd4 transgenes. Mech Dev. 2003;120:325-35 pubmed
    The zebrafish hoxd4a locus was compared to its murine ortholog, Hoxd4. The sequence of regulatory elements, including a DR5 type retinoic acid response element (RARE) required for Hoxd4 neural enhancer activity, are highly conserved...
  13. Yang J, Zeng Z, Wei J, Jiang L, Ma Q, Wu M, et al. Sema4d is required for the development of the hindbrain boundary and skeletal muscle in zebrafish. Biochem Biophys Res Commun. 2013;433:213-9 pubmed publisher
    ..Collectively, these data suggest that sema4d plays an important role in the development of the hindbrain and skeletal muscle. ..
  14. Weicksel S, Gupta A, Zannino D, Wolfe S, SAGERSTROM C. Targeted germ line disruptions reveal general and species-specific roles for paralog group 1 hox genes in zebrafish. BMC Dev Biol. 2014;14:25 pubmed publisher
    ..Lastly, our data reveal independent regulation of hoxb1a expression by retinoic acid and Hoxb1b in zebrafish. ..
  15. Punnamoottil B, Kikuta H, Pezeron G, Erceg J, Becker T, Rinkwitz S. Enhancer detection in zebrafish permits the identification of neuronal subtypes that express Hox4 paralogs. Dev Dyn. 2008;237:2195-208 pubmed publisher
    Activity of zebrafish hoxb4a in the developing brain was analyzed in comparison to hoxa4a and hoxd4a using unique enhancer detection transgenes...
  16. Punnamoottil B, Herrmann C, Pascual Anaya J, D Aniello S, Garcia Fernandez J, Akalin A, et al. Cis-regulatory characterization of sequence conservation surrounding the Hox4 genes. Dev Biol. 2010;340:269-82 pubmed publisher
    ..With the aim to predict enhancers that act on the hoxa4a, hoxb4a, hoxc4a and hoxd4a genes, we used sequence conservation around the Hox4 genes to analyze all fish:human conserved non-coding ..
  17. White R, Nie Q, Lander A, Schilling T. Complex regulation of cyp26a1 creates a robust retinoic acid gradient in the zebrafish embryo. PLoS Biol. 2007;5:e304 pubmed
    ..Such control also provides an explanation for the fact that loss of an endogenous RA gradient can be compensated for by RA that is provided in a spatially uniform manner. ..
  18. Woltering J, Durston A. The zebrafish hoxDb cluster has been reduced to a single microRNA. Nat Genet. 2006;38:601-2 pubmed
  19. Scemama J, Hunter M, McCallum J, Prince V, Stellwag E. Evolutionary divergence of vertebrate Hoxb2 expression patterns and transcriptional regulatory loci. J Exp Zool. 2002;294:285-99 pubmed
  20. Hong S, Dawid I. The transcriptional mediator component Med12 is required for hindbrain boundary formation. PLoS ONE. 2011;6:e19076 pubmed publisher
    ..The kto/med12 mutation results in specific defects of boundary cell formation in the zebrafish hindbrain. ..
  21. Zou S, Jiang X, He Z, Yuan J, Yuan X, Li S. Hox gene clusters in blunt snout bream, Megalobrama amblycephala and comparison with those of zebrafish, fugu and medaka genomes. Gene. 2007;400:60-70 pubmed
    ..Additionally, the relationship between the decrease of GC level and the loss of conservation and function of one of the paralogous genes from twin clusters is discussed. ..