title: Sequestration of retinyl esters is essential for retinoid signaling in the zebrafish embryo.
abstract: For vertebrate development, vitamin A (all-trans retinol) is required in quantitative different amounts and spatiotemporal distribution for the production of retinoic acid, a nuclear hormone receptor ligand, and 11-cis retinal, the chromophore of visual pigments. We show here for zebrafish that embryonic retinoid homeostasis essentially depends on the activity of a leci-thin:retinol acyltransferase (Lratb). During embryogenesis, lratb is expressed in mostly non-overlapping domains opposite to retinal dehydrogenase 2 (raldh2), the key enzyme for retinoic acid synthesis. Blocking retinyl ester formation by a targeted knock down of Lratb results in significantly increased retinoic acid levels, which lead to severe embryonic patterning defects. Thus, we provide evidence that a balanced competition between Lratb and Raldh2 for yolk vitamin A defines embryonic compartments either for retinyl ester or retinoic acid synthesis. This homeostatic mechanism dynamically adjusts embryonic retinoic acid levels for gene regulation, concomitantly sequestering excess yolk vitamin A in the form of retinyl esters for the establishment of larval vision later during development.
authors.affiliation: Department of Neurobiology, Institute of Biology I, Albert-Ludwigs University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Isken
authors.forename: Jochen
authors.initials: J
authors.lastname: Holzschuh
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Lampert
authors.forename: Lara
authors.initials: L
authors.lastname: Fischer
authors.forename: Vitus
authors.initials: V
authors.lastname: Oberhauser
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004330:Drosophila; D004530:Egg Yolk / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D005123:Eye / Q000196:embryology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis / Q000502:physiology; D008969:Molecular Sequence Data; D012172:Retinaldehyde / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*
chemical_list: D004952:Esters; D012176:Retinoids; D014801:Vitamin A; D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; D000217:Acyltransferases; C056942:lecithin-retinol acyltransferase; D012172:Retinaldehyde