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Retinol dehydrogenase 10 is a feedback regulator of retinoic acid signalling during axis formation and patterning of the central nervous system.

Strate, Ina LU ; Tan Grahn, Hooi Min LU ; Iliev, Dobromir LU and Pera, Edgar LU (2009) In Development 136(3). p.461-472
Abstract
Retinoic acid (RA) is an important morphogen that regulates many biological processes, including the development of the central nervous system (CNS). Its synthesis from vitamin A (retinol) occurs in two steps, with the second reaction - catalyzed by retinal dehydrogenases (RALDHs) - long considered to be crucial for tissue-specific RA production in the embryo. We have recently identified the Xenopus homologue of retinol dehydrogenase 10 (XRDH10) that mediates the first step in RA synthesis from retinol to retinal. XRDH10 is specifically expressed in the dorsal blastopore lip and in other domains of the early embryo that partially overlap with XRALDH2 expression. We show that endogenous RA suppresses XRDH10 gene expression, suggesting... (More)
Retinoic acid (RA) is an important morphogen that regulates many biological processes, including the development of the central nervous system (CNS). Its synthesis from vitamin A (retinol) occurs in two steps, with the second reaction - catalyzed by retinal dehydrogenases (RALDHs) - long considered to be crucial for tissue-specific RA production in the embryo. We have recently identified the Xenopus homologue of retinol dehydrogenase 10 (XRDH10) that mediates the first step in RA synthesis from retinol to retinal. XRDH10 is specifically expressed in the dorsal blastopore lip and in other domains of the early embryo that partially overlap with XRALDH2 expression. We show that endogenous RA suppresses XRDH10 gene expression, suggesting negative-feedback regulation. In mRNA-injected Xenopus embryos, XRDH10 mimicked RA responses, influenced the gene expression of organizer markers, and synergized with XRALDH2 in posteriorizing the developing brain. Knockdown of XRDH10 and XRALDH2 by specific antisense morpholino oligonucleotides had the opposite effects on organizer gene expression, and caused a ventralized phenotype and anteriorization of the brain. These data indicate that the conversion of retinol into retinal is a developmentally controlled step involved in specification of the dorsoventral and anteroposterior body axes, as well as in pattern formation of the CNS. We suggest that the combinatorial gene expression and concerted action of XRDH10 and XRALDH2 constitute a ;biosynthetic enzyme code' for the establishment of a morphogen gradient in the embryo. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Development
volume
136
issue
3
pages
461 - 472
publisher
Society for International Development
external identifiers
  • wos:000262409500012
  • pmid:19141675
  • scopus:64549139013
ISSN
1477-9129
DOI
10.1242/dev.024901
language
English
LU publication?
yes
id
b97c48cf-ca7c-4418-8def-dd7c997bf16a (old id 1289722)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19141675?dopt=Abstract
date added to LUP
2009-02-04 11:23:23
date last changed
2017-07-02 04:36:24
@article{b97c48cf-ca7c-4418-8def-dd7c997bf16a,
  abstract     = {Retinoic acid (RA) is an important morphogen that regulates many biological processes, including the development of the central nervous system (CNS). Its synthesis from vitamin A (retinol) occurs in two steps, with the second reaction - catalyzed by retinal dehydrogenases (RALDHs) - long considered to be crucial for tissue-specific RA production in the embryo. We have recently identified the Xenopus homologue of retinol dehydrogenase 10 (XRDH10) that mediates the first step in RA synthesis from retinol to retinal. XRDH10 is specifically expressed in the dorsal blastopore lip and in other domains of the early embryo that partially overlap with XRALDH2 expression. We show that endogenous RA suppresses XRDH10 gene expression, suggesting negative-feedback regulation. In mRNA-injected Xenopus embryos, XRDH10 mimicked RA responses, influenced the gene expression of organizer markers, and synergized with XRALDH2 in posteriorizing the developing brain. Knockdown of XRDH10 and XRALDH2 by specific antisense morpholino oligonucleotides had the opposite effects on organizer gene expression, and caused a ventralized phenotype and anteriorization of the brain. These data indicate that the conversion of retinol into retinal is a developmentally controlled step involved in specification of the dorsoventral and anteroposterior body axes, as well as in pattern formation of the CNS. We suggest that the combinatorial gene expression and concerted action of XRDH10 and XRALDH2 constitute a ;biosynthetic enzyme code' for the establishment of a morphogen gradient in the embryo.},
  author       = {Strate, Ina and Tan Grahn, Hooi Min and Iliev, Dobromir and Pera, Edgar},
  issn         = {1477-9129},
  language     = {eng},
  number       = {3},
  pages        = {461--472},
  publisher    = {Society for International Development},
  series       = {Development},
  title        = {Retinol dehydrogenase 10 is a feedback regulator of retinoic acid signalling during axis formation and patterning of the central nervous system.},
  url          = {http://dx.doi.org/10.1242/dev.024901},
  volume       = {136},
  year         = {2009},
}