|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 28 February 2007
doi: 10.1242/dev.02815
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Wellcome Trust Functional Genomics Development Initiative, MRC Centre for
Developmental Neurobiology, 4th Floor New Hunt's House, King's College London,
Guy's Campus, London SE1 1UL, UK.
2 MRC Centre for Developmental Neurobiology, 4th Floor New Hunt's House, King's
College London, Guy's Campus, London SE1 1UL, UK.
* Author for correspondence (e-mail: andrew.lumsden{at}kcl.ac.uk)
Accepted 15 December 2006
Several independent lines of evidence have revealed an instructive role for retinoic acid (RA) signalling in the establishment of normal pattern and cellular specification of the vertebrate embryo. Molecular analyses have previously identified the major RA-synthesising (RALDH1-3) and RA-degrading (CYP26A-C1) enzymes as well as other components involved in RA processing (e.g. CRABP). Although the majority of the early effects of RA can be attributed to the activity of RALDH2, many other effects are suggestive of the presence of an as yet unidentified RA source. Here we describe the identification, expression, biochemistry and functional analysis of CYP1B1, a member of the cytochrome p450 family of mono-oxygenases, and provide evidence that it contributes to RA synthesis during embryonic patterning. We present in vitro biochemical data demonstrating that this enzyme can generate both all-trans-retinal (t-RAL) and all-trans-retinoic acid (t-RA) from the precursor all-trans-retinol (t-ROH), but unlike the CYP26s, CYP1B1 cannot degrade t-RA. In particular, we focussed on the capacity of CYP1B1 to regulate the molecular mechanisms associated with dorsoventral patterning of the neural tube and acquisition of motor neuron progenitor domain identity. Concordant with its sites of expression and biochemistry, data are presented demonstrating that CYP1B1 is capable of eliciting responses that are consistent with the production of RA. Taken together, we propose that these data provide strong support for CYP1B1 being one of the RALDH-independent components by which embryos direct RA-mediated patterning.
Key words: Cyp1B1, Retinoic acid, Hindbrain, Motor neurons, Dorsoventral, Shh, Hoxb1, Chick
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Yokota, H. Takeuchi, N. Maeda, Y. Ohoka, C. Kato, S.-Y. Song, and M. Iwata GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity Int. Immunol., April 1, 2009; 21(4): 361 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Conway, Y. Sakurai, D. Weiss, J. D. Vega, W. R. Taylor, H. Jo, S. G. Eskin, C. B. Marcus, and L. V. McIntire Expression of CYP1A1 and CYP1B1 in human endothelial cells: regulation by fluid shear stress Cardiovasc Res, March 1, 2009; 81(4): 669 - 677. [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]
|
|
|
|
 |
|
 Y. Tang, E. A. Scheef, S. Wang, C. M. Sorenson, C. B. Marcus, C. R. Jefcoate, and N. Sheibani CYP1B1 expression promotes the proangiogenic phenotype of endothelium through decreased intracellular oxidative stress and thrombospondin-2 expression Blood, January 15, 2009; 113(3): 744 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Halberg, M. C. Larsen, T. L. Elmergreen, A. Y. Ko, A. A. Irving, L. Clipson, and C. R. Jefcoate Cyp1b1 Exerts Opposing Effects on Intestinal Tumorigenesis via Exogenous and Endogenous Substrates Cancer Res., September 15, 2008; 68(18): 7394 - 7402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Yin, H.-P. Tseng, H.-Y. Chung, C.-Y. Ko, W.-S. Tzou, D. R. Buhler, and C.-H. Hu Influence of TCDD on Zebrafish CYP1B1 Transcription during Development Toxicol. Sci., May 1, 2008; 103(1): 158 - 168. [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]
|
|
|
|
 |
|
 S. Chakrabarti, K. R. Devi, S. Komatireddy, K. Kaur, R. S. Parikh, A. K. Mandal, G. Chandrasekhar, and R. Thomas Glaucoma-Associated CYP1B1 Mutations Share Similar Haplotype Backgrounds in POAG and PACG Phenotypes Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5439 - 5444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Jonsson, M. J. Jenny, B. R. Woodin, M. E. Hahn, and J. J. Stegeman Role of AHR2 in the Expression of Novel Cytochrome P450 1 Family Genes, Cell Cycle Genes, and Morphological Defects in Developing Zebra Fish Exposed to 3,3',4,4',5-Pentachlorobiphenyl or 2,3,7,8-Tetrachlorodibenzo-p-dioxin Toxicol. Sci., November 1, 2007; 100(1): 180 - 193. [Abstract] [Full Text] [PDF]
|
|
