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

Yasuo Sakai, Tuanlian Luo, Peter John Andrew McCaffery, Hiroshi Hamada, Ursula C Dräger

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)143-157
Number of pages15
JournalDevelopmental Biology
Volume276
Issue number1
DOIs
Publication statusPublished - 1 Dec 2004

Keywords

  • animals
  • body patterning
  • cytochrome P-450 enzyme system
  • eye
  • gene expression regulation, enzymologic
  • reporter genes
  • mice
  • knockout mice
  • temporal retina
  • tretinoin
  • beta-galactosidase
  • developing mouse retina
  • dorsoventral axis
  • CYP26A1
  • CYP26B1
  • CYP26C1
  • retinoic acid homeostasis
  • visual streak
  • anisotropy
  • moon illusion
  • retinaldehyde dehydrogenase
  • aldehyde dehydrogenase
  • human cytochrome-P450
  • synthesizing enzyme
  • metabolizing enzyme
  • active repression
  • genetic evidence
  • ventral retina

Cite this

CYP26A1 and CYP26C1 cooperate in degrading retinoic acid within the equatorial retina during later eye development. / Sakai, Yasuo; Luo, Tuanlian; McCaffery, Peter John Andrew; Hamada, Hiroshi; Dräger, Ursula C.

In: Developmental Biology, Vol. 276, No. 1, 01.12.2004, p. 143-157.

Research output: Contribution to journalArticle

Sakai, Yasuo ; Luo, Tuanlian ; McCaffery, Peter John Andrew ; Hamada, Hiroshi ; Dräger, Ursula C. / CYP26A1 and CYP26C1 cooperate in degrading retinoic acid within the equatorial retina during later eye development. In: Developmental Biology. 2004 ; Vol. 276, No. 1. pp. 143-157.
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AU - Luo, Tuanlian

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AU - Hamada, Hiroshi

AU - Dräger, Ursula C

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N2 - 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.

AB - 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.

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