This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fan, X.
Right arrow Articles by Duester, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fan, X.
Right arrow Articles by Duester, G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2003, p. 4637-4648, Vol. 23, No. 13
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.13.4637-4648.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Targeted Disruption of Aldh1a1 (Raldh1) Provides Evidence for a Complex Mechanism of Retinoic Acid Synthesis in the Developing Retina

Xiaohong Fan,1 Andrei Molotkov,1 Shin-Ichi Manabe,2 Christine M. Donmoyer,3 Louise Deltour,1,{dagger} Mario H. Foglio,1,{ddagger} Arnold E. Cuenca,1 William S. Blaner,3 Stuart A. Lipton,2 and Gregg Duester1*

OncoDevelopmental Biology Program,1 Center for Neuroscience and Aging, Burnham Institute, La Jolla, California,2 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York3

Received 13 January 2003/ Returned for modification 17 March 2003/ Accepted 8 April 2003

Genetic studies have shown that retinoic acid (RA) signaling is required for mouse retina development, controlled in part by an RA-generating aldehyde dehydrogenase encoded by Aldh1a2 (Raldh2) expressed transiently in the optic vesicles. We examined the function of a related gene, Aldh1a1 (Raldh1), expressed throughout development in the dorsal retina. Raldh1-/- mice are viable and exhibit apparently normal retinal morphology despite a complete absence of Raldh1 protein in the dorsal neural retina. RA signaling in the optic cup, detected by using a RARE-lacZ transgene, is not significantly altered in Raldh1-/- embryos at embryonic day 10.5, possibly due to normal expression of Aldh1a3 (Raldh3) in dorsal retinal pigment epithelium and ventral neural retina. However, at E16.5 when Raldh3 is expressed ventrally but not dorsally, Raldh1-/- embryos lack RARE-lacZ expression in the dorsal retina and its retinocollicular axonal projections, whereas normal RARE-lacZ expression is detected in the ventral retina and its axonal projections. Retrograde labeling of adult Raldh1-/- retinal ganglion cells indicated that dorsal retinal axons project to the superior colliculus, and electroretinography revealed no defect of adult visual function, suggesting that dorsal RA signaling is unnecessary for retinal ganglion cell axonal outgrowth. We observed that RA synthesis in liver of Raldh1-/- mice was greatly reduced, thus showing that Raldh1 indeed participates in RA synthesis in vivo. Our findings suggest that RA signaling may be necessary only during early stages of retina development and that if RA synthesis is needed in dorsal retina, it is catalyzed by multiple enzymes, including Raldh1.

* Corresponding author. Mailing address: Burnham Institute, OncoDevelopmental Biology Program, 10901 North Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 646-3138. Fax: (858) 646-3195. E-mail: duester{at}burnham.org.

{dagger} Present address: Institut Cochin, INSERM U567, CNRS UMR 8104, Université René Descartes, Département Génétique, Développement et Pathologie Moléculaire, 75014 Paris, France.

{ddagger} Present address: Centre National de Génotypage, 91006 Evry Cedex, France.

Molecular and Cellular Biology, July 2003, p. 4637-4648, Vol. 23, No. 13
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.13.4637-4648.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Levi, B. P., Yilmaz, O. H., Duester, G., Morrison, S. J. (2009). Aldehyde dehydrogenase 1a1 is dispensable for stem cell function in the mouse hematopoietic and nervous systems. Blood 113: 1670-1680 [Abstract] [Full Text]  
  • Pang, W., Li, C., Zhao, Y., Wang, S., Dong, W., Jiang, P., Zhang, J. (2008). The Environmental Light Influences the Circulatory Levels of Retinoic Acid and Associates with Hepatic Lipid Metabolism. Endocrinology 149: 6336-6342 [Abstract] [Full Text]  
  • Lassen, N., Bateman, J. B., Estey, T., Kuszak, J. R., Nees, D. W., Piatigorsky, J., Duester, G., Day, B. J., Huang, J., Hines, L. M., Vasiliou, V. (2007). Multiple and Additive Functions of ALDH3A1 and ALDH1A1: CATARACT PHENOTYPE AND OCULAR OXIDATIVE DAMAGE IN Aldh3a1(-/-)/Aldh1a1(-/-) KNOCK-OUT MICE. J. Biol. Chem. 282: 25668-25676 [Abstract] [Full Text]  
  • Jacobs, F. M. J., Smits, S. M., Noorlander, C. W., von Oerthel, L., van der Linden, A. J. A., Burbach, J. P. H., Smidt, M. P. (2007). Retinoic acid counteracts developmental defects in the substantia nigra caused by Pitx3 deficiency. Development 134: 2673-2684 [Abstract] [Full Text]  
  • Marchitti, S. A., Deitrich, R. A., Vasiliou, V. (2007). Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase. Pharmacol. Rev. 59: 125-150 [Abstract] [Full Text]  
  • Sandell, L. L., Sanderson, B. W., Moiseyev, G., Johnson, T., Mushegian, A., Young, K., Rey, J.-P., Ma, J.-x., Staehling-Hampton, K., Trainor, P. A. (2007). RDH10 is essential for synthesis of embryonic retinoic acid and is required for limb, craniofacial, and organ development. Genes Dev. 21: 1113-1124 [Abstract] [Full Text]  
  • Gu, X., Xu, F., Song, W., Wang, X., Hu, P., Yang, Y., Gao, X., Zhao, Q. (2006). A Novel Cytochrome P450, Zebrafish Cyp26D1, Is Involved in Metabolism of All-trans Retinoic Acid. Mol. Endocrinol. 20: 1661-1672 [Abstract] [Full Text]  
  • Molotkov, A., Molotkova, N., Duester, G. (2006). Retinoic acid guides eye morphogenetic movements via paracrine signaling but is unnecessary for retinal dorsoventral patterning. Development 133: 1901-1910 [Abstract] [Full Text]  
  • Vernet, N., Dennefeld, C., Rochette-Egly, C., Oulad-Abdelghani, M., Chambon, P., Ghyselinck, N. B., Mark, M. (2006). Retinoic Acid Metabolism and Signaling Pathways in the Adult and Developing Mouse Testis. Endocrinology 147: 96-110 [Abstract] [Full Text]  
  • Sen, J., Harpavat, S., Peters, M. A., Cepko, C. L. (2005). Retinoic acid regulates the expression of dorsoventral topographic guidance molecules in the chick retina. Development 132: 5147-5159 [Abstract] [Full Text]  
  • Matt, N., Dupe, V., Garnier, J.-M., Dennefeld, C., Chambon, P., Mark, M., Ghyselinck, N. B. (2005). Retinoic acid-dependent eye morphogenesis is orchestrated by neural crest cells. Development 132: 4789-4800 [Abstract] [Full Text]  
  • Li, X.-H., Kakkad, B., Ong, D. E. (2004). Estrogen Directly Induces Expression of Retinoic Acid Biosynthetic Enzymes, Compartmentalized between the Epithelium and Underlying Stromal Cells in Rat Uterus. Endocrinology 145: 4756-4762 [Abstract] [Full Text]  
  • Mic, F. A., Sirbu, I. O., Duester, G. (2004). Retinoic Acid Synthesis Controlled by Raldh2 Is Required Early for Limb Bud Initiation and Then Later as a Proximodistal Signal during Apical Ectodermal Ridge Formation. J. Biol. Chem. 279: 26698-26706 [Abstract] [Full Text]  
  • Dupe, V., Matt, N., Garnier, J.-M., Chambon, P., Mark, M., Ghyselinck, N. B. (2003). A newborn lethal defect due to inactivation of retinaldehyde dehydrogenase type 3 is prevented by maternal retinoic acid treatment. Proc. Natl. Acad. Sci. USA 100: 14036-14041 [Abstract] [Full Text]  
  • Molotkov, A., Duester, G. (2003). Genetic Evidence That Retinaldehyde Dehydrogenase Raldh1 (Aldh1a1) Functions Downstream of Alcohol Dehydrogenase Adh1 in Metabolism of Retinol to Retinoic Acid. J. Biol. Chem. 278: 36085-36090 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»