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PMID: 17767158 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Modulation of morphogenesis by noncanonical Wnt signaling requires ATF/CREB family-mediated transcriptional activation of TGFbeta2.

Nature genetics ·Vol. 39 ·No. 10 ·2007-10-00 ·Pages 1225-34

Zhou W, Lin L, Majumdar A, Li X, Zhang X, Liu W, Etheridge L, Shi Y, Martin J, Van de Ven W, Kaartinen V, Wynshaw-Boris A, McMahon AP, Rosenfeld MG, Evans SM

Abstract

Transcriptional readout downstream of canonical Wnt signaling is known to be mediated by beta-catenin activation of well-described targets, but potential transcriptional readout in response to noncanonical Wnt signaling remains poorly understood. Here, we define a transcriptional pathway important in noncanonical Wnt signaling. We have found that Wnt11 is a direct target of a canonical beta-catenin pathway in developing heart and that Wnt11 mutants show cardiac outflow tract defects. We provide genetic and biochemical evidence thatWnt11 signaling affects extracellular matrix composition, cytoskeletal rearrangements and polarized cell movement required for morphogenesis of the cardiac outflow tract. Notably, transforming growth factor beta2 (TGFbeta2), a key effector of organ morphogenesis, is regulated by Wnt11-mediated noncanonical signaling in developing heart and somites via one or more activating transcription factor (ATF)/cyclic AMP response element binding protein (CREB) family members. Thus, we propose that transcriptional readout mediated at least in part by a Wnt11 --> ATF/CREB --> TGFbeta2 pathway is critical in regulating morphogenesis in response to noncanonical Wnt signaling.

MeSH Terms
Activating Transcription Factors/metabolism Animals Base Sequence Blood Proteins/metabolism Cell Lineage Cyclic AMP Response Element-Binding Protein/metabolism Down-Regulation Heart/embryology,growth & development Homeodomain Proteins/metabolism Humans Mice Molecular Sequence Data Morphogenesis/physiology Signal Transduction Transcription Factors/metabolism Transcriptional Activation Transforming Growth Factor beta2/genetics,metabolism Wnt Proteins/genetics,metabolism beta Catenin/metabolism
Chemicals
Activating Transcription Factors Blood Proteins Creb1 protein, mouse Cyclic AMP Response Element-Binding Protein Homeodomain Proteins Tgfb2 protein, mouse Transcription Factors Transforming Growth Factor beta2 Wnt Proteins Wnt11 protein, mouse beta Catenin homeobox protein PITX2
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Zhou Wenlai
Howard Hughes Medical Institute and Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Lin Lizhu
Majumdar Arindam
Li Xue
Zhang Xiaoxue
Liu Wei
Etheridge Leah
Shi Yunqing
Martin James
Van de Ven Wim
Kaartinen Vesa
Wynshaw-Boris Anthony
McMahon Andrew P
Rosenfeld Michael G
Evans Sylvia M
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng2112
Published
2007-10-00
Epub
2007-00-02
Pages
1225-34
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC5578467
Subset
IM
Grants
NHLBI NIH HHS · HL66276 · United States
NIDDK NIH HHS · R37 DK054364 · United States
NIDDK NIH HHS · R01 DK054364 · United States
NIDDK NIH HHS · DK 064744 · United States
NHLBI NIH HHS · HL65445 · United States
NHLBI NIH HHS · R01 HL065445 · United States
NIDDK NIH HHS · DK18477 · United States
NHLBI NIH HHS · R01 HL074066 · United States
NIH HHS · DP1 OD006428 · United States
NHLBI NIH HHS · HL74066 · United States
NIDDK NIH HHS · R01 DK018477 · United States
NHLBI NIH HHS · R01 HL070867 · United States
NHLBI NIH HHS · HL70867 · United States
NINDS NIH HHS · R01 NS073159 · United States
NIDDK NIH HHS · K01 DK064744 · United States
NIDDK NIH HHS · DK054364 · United States
NHLBI NIH HHS · R01 HL066276 · United States
NHLBI NIH HHS · DP1 HL117649 · United States
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GENBANK
AA511462, BF135240, BQ713524, BQ944558
External Links
PubMed source DOI: 10.1038/ng2112 PMC Full Text View journal details
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