QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online December 12, 2006
doi: 10.1242/10.1242/dev.02706

This Article Figures Only Full Text Full Text (PDF) Supplementary Material Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hernandez, R. E. Articles by Moens, C. B. Search for Related Content PubMed PubMed Citation Articles by Hernandez, R. E. Articles by Moens, C. B. Social Bookmarking                         What's this?

Cyp26 enzymes generate the retinoic acid response pattern necessary for hindbrain development

Rafael E. Hernandez^1,2,*, Aaron P. Putzke^1,*, Jonathan P. Myers^1,, Lilyana Margaretha¹ and Cecilia B. Moens^1,

¹ HHMI and Division of Basic Science, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109-1024, USA.
² Medical Scientist Training Program and Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98195-7470, USA.

Author for correspondence (e-mail: cmoens{at}fhcrc.org)

Accepted 18 October 2006

Retinoic acid (RA) is essential for normal vertebrate development, including the patterning of the central nervous system. During early embryogenesis, RA is produced in the trunk mesoderm through the metabolism of vitamin A derived from the maternal diet and behaves as a morphogen in the developing hindbrain where it specifies nested domains of Hox gene expression. The loss of endogenous sources of RA can be rescued by treatment with a uniform concentration of exogenous RA, indicating that domains of RA responsiveness can be shaped by mechanisms other than the simple diffusion of RA from a localized posterior source. Here, we show that the cytochrome p450 enzymes of the Cyp26 class, which metabolize RA into polar derivatives, function redundantly to shape RA-dependent gene-expression domains during hindbrain development. In zebrafish embryos depleted of the orthologs of the three mammalian CYP26 genes CYP26A1, CYP26B1 and CYP26C1, the entire hindbrain expresses RA-responsive genes that are normally restricted to nested domains in the posterior hindbrain. Furthermore, we show that Cyp26 enzymes are essential for exogenous RA to rescue hindbrain patterning in RA-depleted embryos. We present a `gradient-free' model for hindbrain patterning in which differential RA responsiveness along the hindbrain anterior-posterior axis is shaped primarily by the dynamic expression of RA-degrading enzymes.

Key words: Retinoic acid, Hindbrain, Cyp26, Hox, Morphogen, Zebrafish

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in Development:

Degrading uniformity in hindbrain patterning

Development 2007 134: e102. [Full Text]  

This article has been cited by other articles:

				D. Maurus and W. A. Harris Zic-associated holoprosencephaly: zebrafish Zic1 controls midline formation and forebrain patterning by regulating Nodal, Hedgehog, and retinoic acid signaling Genes & Dev., June 15, 2009; 23(12): 1461 - 1473. [Abstract] [Full Text] [PDF]

				K. Schmidt, C. Hughes, J. A. Chudek, S. R. Goodyear, R. M. Aspden, R. Talbot, T. E. Gundersen, R. Blomhoff, C. Henderson, C. R. Wolf, et al. Cholesterol Metabolism: the Main Pathway Acting Downstream of Cytochrome P450 Oxidoreductase in Skeletal Development of the Limb Mol. Cell. Biol., May 15, 2009; 29(10): 2716 - 2729. [Abstract] [Full Text] [PDF]

				M. D. Kinkel, E. M. Sefton, Y. Kikuchi, T. Mizoguchi, A. B. Ward, and V. E. Prince Cyp26 enzymes function in endoderm to regulate pancreatic field size PNAS, May 12, 2009; 106(19): 7864 - 7869. [Abstract] [Full Text] [PDF]

				I. Strate, T. H. Min, D. Iliev, and E. M. Pera Retinol dehydrogenase 10 is a feedback regulator of retinoic acid signalling during axis formation and patterning of the central nervous system Development, February 1, 2009; 136(3): 461 - 472. [Abstract] [Full Text] [PDF]

				K. S. Imai, A. Stolfi, M. Levine, and Y. Satou Gene regulatory networks underlying the compartmentalization of the Ciona central nervous system Development, January 15, 2009; 136(2): 285 - 293. [Abstract] [Full Text] [PDF]

				K. Laue, M. Janicke, N. Plaster, C. Sonntag, and M. Hammerschmidt Restriction of retinoic acid activity by Cyp26b1 is required for proper timing and patterning of osteogenesis during zebrafish development Development, November 15, 2008; 135(22): 3775 - 3787. [Abstract] [Full Text] [PDF]

				K. M. Spoorendonk, J. Peterson-Maduro, J. Renn, T. Trowe, S. Kranenbarg, C. Winkler, and S. Schulte-Merker Retinoic acid and Cyp26b1 are critical regulators of osteogenesis in the axial skeleton Development, November 15, 2008; 135(22): 3765 - 3774. [Abstract] [Full Text] [PDF]

				P. A. Gongal and A. J. Waskiewicz Zebrafish model of holoprosencephaly demonstrates a key role for TGIF in regulating retinoic acid metabolism Hum. Mol. Genet., February 14, 2008; 17(4): 525 - 538. [Abstract] [Full Text] [PDF]

				J. Bowles and P. Koopman Retinoic acid, meiosis and germ cell fate in mammals Development, October 1, 2007; 134(19): 3401 - 3411. [Abstract] [Full Text] [PDF]

				L. L. Sandell, B. W. Sanderson, G. Moiseyev, T. Johnson, A. Mushegian, K. Young, J.-P. Rey, J.-x. Ma, K. Staehling-Hampton, and P. A. Trainor RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development Genes & Dev., May 1, 2007; 21(9): 1113 - 1124. [Abstract] [Full Text] [PDF]