HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 49, 51581-51589, December 3, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/49/51581    most recent M408830200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nadauld, L. D. Articles by Jones, D. A. Search for Related Content PubMed PubMed Citation Articles by Nadauld, L. D. Articles by Jones, D. A. Social Bookmarking                      What's this?

Adenomatous Polyposis Coli Control of Retinoic Acid Biosynthesis Is Critical for Zebrafish Intestinal Development and Differentiation^*

Lincoln D. Nadauld, Imelda T. Sandoval¶, Stephanie Chidester, H. Joseph Yost, and David A. Jones¶||

From the Departments of Oncological Sciences and ^¶Medicinal Chemistry and the Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112

Mutations in the APC (adenomatous polyposis coli) tumor suppressor gene cause uncontrolled proliferation and impaired differentiation of intestinal epithelial cells. Recent studies indicate that human colon adenomas and carcinomas lack retinol dehydrogenases (RDHs) and that APC regulates the expression of human RDHL. These data suggest a model wherein APC controls enterocyte differentiation by controlling retinoic acid production. However, the importance of APC and retinoic acid in mediating control of normal enterocyte development and differentiation remains unclear. To examine the relationship between APC and retinoic acid biosynthesis in normal enterocytes, we have identified two novel zebrafish retinol dehydrogenases, termed zRDHA and zRDHB, that show strong expression within the gut of developing zebrafish embryos. Morpholino knockdown of either APC or zRDHB in zebrafish embryos resulted in defects in structures known to require retinoic acid. These defects included cardiac abnormalities, pericardial edema, failed jaw and pectoral fin development, and the absence of differentiated endocrine and exocrine pancreas. In addition, APC or zRDHB morphant fish developed intestines that lacked columnar epithelial cells and failed to express the differentiation marker intestinal fatty acid-binding protein. Treatment of either APC or zRDHB morphant embryos with retinoic acid rescued the defective phenotypes. Downstream of retinoic acid production, we identified hoxc8 as a retinoic acid-induced gene that, when ectopically expressed, rescued phenotypes of APC- and zRDHB-deficient zebrafish. Our data establish a genetic link supporting a critical role for retinoic acid downstream of APC and confirm the importance of retinoic acid in enterocyte differentiation.

Received for publication, August 3, 2004 , and in revised form, August 26, 2004.

^* This work was supported by American Cancer Society Grant RSG-02-141-01, National Cancer Institute Grant CA073992-06A1, and funds from the Huntsman Cancer Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Rm. 5262, Salt Lake City, UT 84112. Tel.: 801-585-6107; E-mail: david.jones{at}hci.utah.edu.

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

This article has been cited by other articles:

				X. Lin and X. Xu Distinct functions of Wnt/{beta}-catenin signaling in KV development and cardiac asymmetry Development, January 15, 2009; 136(2): 207 - 217. [Abstract] [Full Text] [PDF]

				A. L. Eisinger, L. D. Nadauld, D. N. Shelton, S. M. Prescott, D. M. Stafforini, and D. A. Jones Retinoic Acid Inhibits beta-Catenin through Suppression of Cox-2: A ROLE FOR TRUNCATED ADENOMATOUS POLYPOSIS COLI J. Biol. Chem., October 5, 2007; 282(40): 29394 - 29400. [Abstract] [Full Text] [PDF]

				W. Goessling, T. E. North, and L. I. Zon New Waves of Discovery: Modeling Cancer in Zebrafish J. Clin. Oncol., June 10, 2007; 25(17): 2473 - 2479. [Full Text] [PDF]

				L. Wang, Y. Tang, D. C. Rubin, and M. S. Levin Chronically administered retinoic acid has trophic effects in the rat small intestine and promotes adaptation in a resection model of short bowel syndrome Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1559 - G1569. [Abstract] [Full Text] [PDF]

				K. Rai, S. Chidester, C. V. Zavala, E. J. Manos, S. R. James, A. R. Karpf, D. A. Jones, and B. R. Cairns Dnmt2 functions in the cytoplasm to promote liver, brain, and retina development in zebrafish Genes & Dev., February 1, 2007; 21(3): 261 - 266. [Abstract] [Full Text] [PDF]

				L. D. Nadauld, R. Phelps, B. C. Moore, A. Eisinger, I. T. Sandoval, S. Chidester, P. W. Peterson, E. J. Manos, B. Sklow, R. W. Burt, et al. Adenomatous Polyposis Coli Control of C-terminal Binding Protein-1 Stability Regulates Expression of Intestinal Retinol Dehydrogenases J. Biol. Chem., December 8, 2006; 281(49): 37828 - 37835. [Abstract] [Full Text] [PDF]

				K. Rai, L. D. Nadauld, S. Chidester, E. J. Manos, S. R. James, A. R. Karpf, B. R. Cairns, and D. A. Jones Zebra Fish Dnmt1 and Suv39h1 Regulate Organ-Specific Terminal Differentiation during Development. Mol. Cell. Biol., October 1, 2006; 26(19): 7077 - 7085. [Abstract] [Full Text] [PDF]

				L. D. Nadauld, S. Chidester, D. N. Shelton, K. Rai, T. Broadbent, I. T. Sandoval, P. W. Peterson, E. J. Manos, C. M. Ireland, H. J. Yost, et al. Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development PNAS, September 5, 2006; 103(36): 13409 - 13414. [Abstract] [Full Text] [PDF]

				D. N. Shelton, I. T. Sandoval, A. Eisinger, S. Chidester, A. Ratnayake, C. M. Ireland, and D. A. Jones Up-regulation of CYP26A1 in Adenomatous Polyposis Coli-Deficient Vertebrates via a WNT-Dependent Mechanism: Implications for Intestinal Cell Differentiation and Colon Tumor Development. Cancer Res., August 1, 2006; 66(15): 7571 - 7577. [Abstract] [Full Text] [PDF]

				A. L. Eisinger, L. D. Nadauld, D. N. Shelton, P. W. Peterson, R. A. Phelps, S. Chidester, D. M. Stafforini, S. M. Prescott, and D. A. Jones The Adenomatous Polyposis Coli Tumor Suppressor Gene Regulates Expression of Cyclooxygenase-2 by a Mechanism That Involves Retinoic Acid J. Biol. Chem., July 21, 2006; 281(29): 20474 - 20482. [Abstract] [Full Text] [PDF]

				X. He and J. D. Axelrod A WNTer wonderland in Snowbird. Development, July 1, 2006; 133(14): 2597 - 2603. [Abstract] [Full Text] [PDF]

				M. Liden and U. Eriksson Understanding Retinol Metabolism: Structure and Function of Retinol Dehydrogenases J. Biol. Chem., May 12, 2006; 281(19): 13001 - 13004. [Full Text] [PDF]

				L. D. Nadauld, D. N. Shelton, S. Chidester, H. J. Yost, and D. A. Jones The Zebrafish Retinol Dehydrogenase, rdh1l, Is Essential for Intestinal Development and Is Regulated by the Tumor Suppressor Adenomatous Polyposis Coli J. Biol. Chem., August 26, 2005; 280(34): 30490 - 30495. [Abstract] [Full Text] [PDF]