Increased Hox Activity Mimics the Teratogenic Effects of Excess Retinoic Acid Signaling

Overview

Journal Dev Dyn

Publisher Wiley

Specialty Anatomy & Histology

Date 2009 Apr 23

PMID 19384962

Citations 29

Authors

Joshua S Waxman

Deborah Yelon

Affiliations

Soon will be listed here.

Abstract

Excess retinoic acid (RA) signaling can be teratogenic and result in cardiac birth defects, but the cellular and molecular origins of these defects are not well understood. Excessive RA signaling can completely eliminate heart formation in the zebrafish embryo. However, atrial and ventricular cells are differentially sensitive to more modest increases in RA signaling. Increased Hox activity, downstream of RA signaling, causes phenotypes similar to those resulting from excess RA. These results suggest that Hox activity mediates the differential effects of ectopic RA on atrial and ventricular cardiomyocytes and may underlie the teratogenic effects of RA on the heart.

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References

Bruce A, Oates A, Prince V, Ho R . Additional hox clusters in the zebrafish: divergent expression patterns belie equivalent activities of duplicate hoxB5 genes. Evol Dev. 2001; 3(3):127-44. DOI: 10.1046/j.1525-142x.2001.003003127.x. View

Oosterveen T, Niederreither K, Dolle P, Chambon P, Meijlink F, Deschamps J . Retinoids regulate the anterior expression boundaries of 5' Hoxb genes in posterior hindbrain. EMBO J. 2003; 22(2):262-9. PMC: 140104. DOI: 10.1093/emboj/cdg029. View

Keegan B, Feldman J, Begemann G, Ingham P, Yelon D . Retinoic acid signaling restricts the cardiac progenitor pool. Science. 2005; 307(5707):247-9. DOI: 10.1126/science.1101573. View

Mark M, Ghyselinck N, Chambon P . Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu Rev Pharmacol Toxicol. 2006; 46:451-80. DOI: 10.1146/annurev.pharmtox.46.120604.141156. View

Serbedzija G, Chen J, Fishman M . Regulation in the heart field of zebrafish. Development. 1998; 125(6):1095-101. DOI: 10.1242/dev.125.6.1095. View

Ryckebusch L, Wang Z, Bertrand N, Lin S, Chi X, Schwartz R . Retinoic acid deficiency alters second heart field formation. Proc Natl Acad Sci U S A. 2008; 105(8):2913-8. PMC: 2268559. DOI: 10.1073/pnas.0712344105. View

Hernandez R, Putzke A, Myers J, Margaretha L, Moens C . Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development. Development. 2006; 134(1):177-87. PMC: 1765950. DOI: 10.1242/dev.02706. View

Minucci S, Toyama R, Scita G, DeLuca L, Tiara M, Levin A . Retinoid X receptor-selective ligands produce malformations in Xenopus embryos. Proc Natl Acad Sci U S A. 1996; 93(5):1803-7. PMC: 39862. DOI: 10.1073/pnas.93.5.1803. View

Stainier D, Lee R, Fishman M . Cardiovascular development in the zebrafish. I. Myocardial fate map and heart tube formation. Development. 1993; 119(1):31-40. DOI: 10.1242/dev.119.1.31. View

10.

Mably J, Mohideen M, Burns C, Chen J, Fishman M . heart of glass regulates the concentric growth of the heart in zebrafish. Curr Biol. 2003; 13(24):2138-47. DOI: 10.1016/j.cub.2003.11.055. View

11.

Rohrschneider M, Elsen G, Prince V . Zebrafish Hoxb1a regulates multiple downstream genes including prickle1b. Dev Biol. 2007; 309(2):358-72. DOI: 10.1016/j.ydbio.2007.06.012. View

12.

Shimizu T, Bae Y, Hibi M . Cdx-Hox code controls competence for responding to Fgfs and retinoic acid in zebrafish neural tissue. Development. 2006; 133(23):4709-19. DOI: 10.1242/dev.02660. View

13.

Stainier D, Fishman M . Patterning the zebrafish heart tube: acquisition of anteroposterior polarity. Dev Biol. 1992; 153(1):91-101. DOI: 10.1016/0012-1606(92)90094-w. View

14.

Yutzey K, Rhee J, Bader D . Expression of the atrial-specific myosin heavy chain AMHC1 and the establishment of anteroposterior polarity in the developing chicken heart. Development. 1994; 120(4):871-83. DOI: 10.1242/dev.120.4.871. View

15.

Oxtoby E, Jowett T . Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development. Nucleic Acids Res. 1993; 21(5):1087-95. PMC: 309267. DOI: 10.1093/nar/21.5.1087. View

16.

Berdougo E, Coleman H, Lee D, Stainier D, Yelon D . Mutation of weak atrium/atrial myosin heavy chain disrupts atrial function and influences ventricular morphogenesis in zebrafish. Development. 2003; 130(24):6121-9. DOI: 10.1242/dev.00838. View

17.

Waxman J, Keegan B, Roberts R, Poss K, Yelon D . Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish. Dev Cell. 2008; 15(6):923-34. PMC: 2752051. DOI: 10.1016/j.devcel.2008.09.009. View

18.

Searcy R, Yutzey K . Analysis of Hox gene expression during early avian heart development. Dev Dyn. 1998; 213(1):82-91. DOI: 10.1002/(SICI)1097-0177(199809)213:1<82::AID-AJA8>3.0.CO;2-U. View

19.

Holtzman N, Schoenebeck J, Tsai H, Yelon D . Endocardium is necessary for cardiomyocyte movement during heart tube assembly. Development. 2007; 134(12):2379-86. DOI: 10.1242/dev.02857. View

20.

Sharpe J, Nonchev S, Gould A, Whiting J, Krumlauf R . Selectivity, sharing and competitive interactions in the regulation of Hoxb genes. EMBO J. 1998; 17(6):1788-98. PMC: 1170526. DOI: 10.1093/emboj/17.6.1788. View