CYP26A1 and CYP26C1 cooperate in degrading retinoic acid within the equatorial retina during later eye development

Dev Biol. 2004 Dec 1;276(1):143-57. doi: 10.1016/j.ydbio.2004.08.032.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P450 Family 26
  • Eye / embryology*
  • Gene Expression Regulation, Enzymologic
  • Genes, Reporter
  • Mice
  • Mice, Knockout
  • Retina / drug effects
  • Retina / embryology
  • Retina / metabolism*
  • Retinoic Acid 4-Hydroxylase
  • Tretinoin / metabolism*
  • Tretinoin / pharmacology
  • beta-Galactosidase / metabolism


  • Tretinoin
  • Cytochrome P-450 Enzyme System
  • Cyp26a1 protein, mouse
  • Cyp26c1 protein, mouse
  • Cytochrome P450 Family 26
  • Retinoic Acid 4-Hydroxylase
  • beta-Galactosidase