title: CYP26A1 and CYP26C1 cooperate in degrading retinoic acid within the equatorial retina during later eye development.
abstract: In the embryonic mouse retina, retinoic acid (RA) is unevenly distributed along the dorsoventral axis: RA-rich zones in dorsal and ventral retina are separated by a horizontal RA-poor stripe that contains the RA-inactivating enzyme CYP26A1. To explore the developmental role of this arrangement, we studied formation of the retina and its projections in Cyp26a1 null-mutant mice. Expression of several dorsoventral markers was not affected, indicating that CYP26A1 is not required for establishing the dorsoventral retina axis. Analysis of the mutation on a RA-reporter mouse background confirmed, as expected, that the RA-poor stripe was missing in the retina and its projections at the time when the optic axons first grow over the diencephalon. A day later, however, a gap appeared both in retina and retinofugal projections. As explanation, we found that CYP26C1, another RA-degrading enzyme, had emerged centrally in a narrower domain within the RA-poor stripe. While RA applications increased retinal Cyp26a1 expression, they slightly reduced Cyp26c1. These observations indicate that the two enzymes function independently. The safeguard of the RA-poor stripe by two distinct enzymes during later development points to a role in maturation of a significant functional feature like an area of higher visual acuity that develops at its location.
authors.affiliation: Eunice Kennedy Shriver Center at the University of Massachusetts Medical School, Waltham, MA, USA.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sakai
authors.forename: Tuanlian
authors.initials: T
authors.lastname: Luo
authors.forename: Peter
authors.initials: P
authors.lastname: McCaffery
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
authors.forename: Ursula C
authors.initials: UC
authors.lastname: Dräger
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072500:Cytochrome P450 Family 26; D005123:Eye / Q000196:embryology*; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D051379:Mice; D018345:Mice, Knockout; D012160:Retina / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D000072516:Retinoic Acid 4-Hydroxylase; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; C495026:Cyp26c1 protein, mouse; D000072500:Cytochrome P450 Family 26; D000072516:Retinoic Acid 4-Hydroxylase; D001616:beta-Galactosidase