Spatiotemporal manipulation of retinoic acid activity in zebrafish hindbrain development via photo-isomerization

All-trans retinoic acid (RA) is a key player in many developmental pathways. Most methods used to study its effects in development involve continuous all-trans RA activation by incubation in a solution of all-trans RA or by implanting all-trans RA-soaked beads at desired locations in the embryo. Here we show that the UV-driven photo-isomerization of 13-cis RA to the trans-isomer (and vice versa) can be used to non-invasively and quantitatively control the concentration of all-trans RA in a developing embryo in time and space. This facilitates the global or local perturbation of developmental pathways with a pulse of all-trans RA of known concentration or its inactivation by UV illumination. In zebrafish embryos in which endogenous synthesis of all-trans RA is impaired, incubation for as little as 5 minutes in 1 nM all-trans RA (a pulse) or 5 nM 13-cis RA followed by 1-minute UV illumination is sufficient to rescue the development of the hindbrain if performed no later than bud stage. However, if subsequent to this all-trans RA pulse the embryo is illuminated (no later than bud stage) for 1 minute with UV light (to isomerize, i.e. deactivate, all-trans RA), the rescue of hindbrain development is impaired. This suggests that all-trans RA is sequestered in embryos that have been transiently exposed to it. Using 13-cis RA isomerization with UV light, we further show that local illumination at bud stage of the head region (but not the tail) is sufficient to rescue hindbrain formation in embryos whose all-trans RA synthetic pathway has been impaired.

[1]  G. Begemann,et al.  Retinoic acid signaling controls the formation, proliferation and survival of the blastema during adult zebrafish fin regeneration , 2012, Development.

[2]  J. Holdway,et al.  Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration. , 2011, Developmental cell.

[3]  S. Lukyanov,et al.  Fluorescent proteins and their applications in imaging living cells and tissues. , 2010, Physiological reviews.

[4]  A. Oates,et al.  Multiple embryo time-lapse imaging of zebrafish development. , 2009, Methods in molecular biology.

[5]  P. Dollé,et al.  Retinoic acid in development: towards an integrated view , 2008, Nature Reviews Genetics.

[6]  P. Neveu,et al.  A caged retinoic acid for one- and two-photon excitation in zebrafish embryos. , 2008, Angewandte Chemie.

[7]  Olivier Pourquié,et al.  Segmental patterning of the vertebrate embryonic axis , 2008, Nature Reviews Genetics.

[8]  Qing Nie,et al.  Complex Regulation of cyp26a1 Creates a Robust Retinoic Acid Gradient in the Zebrafish Embryo , 2007, PLoS biology.

[9]  Albert Goldbeter,et al.  Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling , 2007, Developmental dynamics : an official publication of the American Association of Anatomists.

[10]  K. Hatta,et al.  Cell tracking using a photoconvertible fluorescent protein , 2006, Nature Protocols.

[11]  G. Duester,et al.  Retinoic-acid signalling in node ectoderm and posterior neural plate directs left–right patterning of somitic mesoderm , 2006, Nature Cell Biology.

[12]  C. Kimmel,et al.  Dynamic and sequential patterning of the zebrafish posterior hindbrain by retinoic acid. , 2005, Developmental biology.

[13]  O. Pourquié,et al.  Retinoic acid coordinates somitogenesis and left–right patterning in vertebrate embryos , 2005, Nature.

[14]  J. Armstrong,et al.  13-cis retinoic acid and isomerisation in paediatric oncology--is changing shape the key to success? , 2005, Biochemical Pharmacology.

[15]  P. Chambon,et al.  Retinoic Acid Controls the Bilateral Symmetry of Somite Formation in the Mouse Embryo , 2005, Science.

[16]  K. Kawakami,et al.  A transposon-mediated gene trap approach identifies developmentally regulated genes in zebrafish. , 2004, Developmental cell.

[17]  A. Meyer,et al.  Beyond the neckless phenotype: influence of reduced retinoic acid signaling on motor neuron development in the zebrafish hindbrain. , 2004, Developmental biology.

[18]  Olivier Pourquié,et al.  Faculty Opinions recommendation of Opposing FGF and retinoid pathways control ventral neural pattern, neuronal differentiation, and segmentation during body axis extension. , 2004 .

[19]  Emily Gale,et al.  Opposing FGF and Retinoid Pathways Control Ventral Neural Pattern, Neuronal Differentiation, and Segmentation during Body Axis Extension , 2003, Neuron.

[20]  Stephen W. Wilson,et al.  Retinoic acid signalling in the zebrafish embryo is necessary during pre-segmentation stages to pattern the anterior-posterior axis of the CNS and to induce a pectoral fin bud. , 2002, Development.

[21]  N. Hopkins,et al.  vhnf1, the MODY5 and familial GCKD-associated gene, regulates regional specification of the zebrafish gut, pronephros, and hindbrain. , 2001, Genes & development.

[22]  M. Newcomer,et al.  Epididymal retinoic acid-binding protein. , 2000, Biochimica et biophysica acta.

[23]  U. Dräger,et al.  Retinoids in embryonal development. , 2000, Physiological reviews.

[24]  G. Hauptmann,et al.  Regulatory gene expression patterns reveal transverse and longitudinal subdivisions of the embryonic zebrafish forebrain , 2000, Mechanisms of Development.

[25]  B. Thisse,et al.  Ontogeny and behaviour of early macrophages in the zebrafish embryo. , 1999, Development.

[26]  D. Levinthal,et al.  Distinct Roles for Cellular Retinoic Acid-binding Proteins I and II in Regulating Signaling by Retinoic Acid* , 1999, The Journal of Biological Chemistry.

[27]  P. Chambon,et al.  Embryonic retinoic acid synthesis is essential for early mouse post-implantation development , 1999, Nature Genetics.

[28]  E. Sonneveld,et al.  The distribution of endogenous retinoic acid in the chick embryo: implications for developmental mechanisms. , 1998, Development.

[29]  H P Koeffler,et al.  Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  R. Ho,et al.  Zebrafish hox genes: expression in the hindbrain region of wild-type and mutants of the segmentation gene, valentino. , 1998, Development.

[31]  M. Farrell,et al.  Promoter analysis in living zebrafish embryos identifies a cis-acting motif required for neuronal expression of GATA-2. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Zeitlinger,et al.  Endogenous retinoids in the zebrafish embryo and adult , 1996, Developmental dynamics : an official publication of the American Association of Anatomists.

[33]  P. Bernstein,et al.  Photoaffinity labeling of retinoic acid-binding proteins. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[34]  M. Westerfield.  The zebrafish book : a guide for the laboratory use of zebrafish (Danio rerio) , 1995 .

[35]  D. Bempong,et al.  Separation of 13-cis and all-trans retinoic acid and their photodegradation products using capillary zone electrophoresis and micellar electrokinetic chromatography (MEC). , 1993, Journal of pharmaceutical and biomedical analysis.

[36]  E. Oxtoby,et al.  Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development. , 1993, Nucleic acids research.

[37]  P Chambon,et al.  Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids. , 1993, Proceedings of the National Academy of Sciences of the United States of America.