title: Spatiotemporal manipulation of retinoic acid activity in zebrafish hindbrain development via photo-isomerization.
abstract: 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.
authors.affiliation: Laboratoire de Physique Statistique, Ecole Normale Supérieure, UPMC Université Paris 06, Université Paris Diderot, CNRS UMR8550, 24 rue Lhomond, 75005 Paris, France.
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Feng
authors.forename: Deepak
authors.initials: D
authors.lastname: Sinha
authors.forename: Bertrand
authors.initials: B
authors.lastname: Ducos
authors.forename: Yuval
authors.initials: Y
authors.lastname: Ebenstein
authors.forename: Arbel D
authors.initials: AD
authors.lastname: Tadmor
authors.forename: Carole
authors.initials: C
authors.lastname: Gauron
authors.forename: Thomas
authors.initials: T
authors.lastname: Le Saux
authors.forename: Shuo
authors.initials: S
authors.lastname: Lin
authors.forename: Shimon
authors.initials: S
authors.lastname: Weiss
authors.forename: Sophie
authors.initials: S
authors.lastname: Vriz
authors.forename: Ludovic
authors.initials: L
authors.lastname: Jullien
authors.forename: David
authors.initials: D
authors.lastname: Bensimon
mesh_terms: D000818:Animals; D015474:Isotretinoin / Q000737:chemistry / Q000378:metabolism; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism* / Q000528:radiation effects; D014212:Tretinoin / Q000737:chemistry / Q000378:metabolism*; D014466:Ultraviolet Rays; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*
chemical_list: D014212:Tretinoin; D015474:Isotretinoin