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

Lijun Xu, Zhiping Feng*, Deepak Sinha, Bertrand Ducos, Yuval Ebenstein, Arbel D. Tadmor, Carole Gauron, Thomas le Saux, Shuo Lin, Shimon Weiss, Sophie Vriz, Ludovic Jullien, David Bensimon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)3355-3362
Number of pages8
JournalDevelopment (Cambridge)
Issue number18
StatePublished - 15 Sep 2012
Externally publishedYes


  • Hindbrain
  • Retinoic acid
  • Spatiotemporal control
  • Zebrafish


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