CYP26A1 and CYP26C1 cooperate in degrading retinoic acid within the equatorial retina during later eye development.
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.
Sakai
Yasuo
Y
Eunice Kennedy Shriver Center at the University of Massachusetts Medical School, Waltham, MA, USA.
Luo
Tuanlian
T
McCaffery
Peter
P
Hamada
Hiroshi
H
Dräger
Ursula C
UC
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
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