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PMID: 15096597 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 17 ·2004-04-27 ·Pages 6502-7

Akiyama H, Chaboissier MC, Behringer RR, Rowitch DH, Schedl A, Epstein JA, de Crombrugghe B

Abstract

Epithelial-mesenchymal transformation is a critical developmental process reiterated in multiple organs throughout embryogenesis. Formation of endocardial cushions, primordia of valves and septa, is a classic example of epithelial-mesenchymal transformation. Several gene mutations are known to affect cardiac valve formation. Sox9 is activated when endocardial endothelial cells undergo mesenchymal transformation and migrate into an extracellular matrix, called cardiac jelly, to form endocardial cushions. In Sox9-null mutants, endocardial cushions are markedly hypoplastic. In these mutants, Nfatc1 is ectopically expressed and no longer restricted to endothelial cells. Further, Sox9-deficient endocardial mesenchymal cells fail to express ErbB3, which is required for endocardial cushion cell differentiation and proliferation. Our results reveal a succession of molecular steps in the pathway of endocardial cushion development. We propose that loss of Sox9 inhibits epithelial-mesenchymal transformation after delamination and initial migration, but before definitive mesenchymal transformation.

MeSH Terms
Animals Cell Division Female Heart Septum/cytology,embryology Heart Valves/cytology,embryology High Mobility Group Proteins/genetics,physiology Mesoderm Mice Mice, Transgenic Mutation Pregnancy Receptor, ErbB-3/genetics SOX9 Transcription Factor Transcription Factors/genetics,physiology
Chemicals
High Mobility Group Proteins SOX9 Transcription Factor Sox9 protein, mouse Transcription Factors Receptor, ErbB-3
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Akiyama Haruhiko
Department of Molecular Genetics, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Chaboissier Marie-Christine
Behringer Richard R
Rowitch David H
Schedl Andreas
Epstein Jonathan A
de Crombrugghe Benoit
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0401711101
Published
2004-04-27
Epub
2004-00-19
Pages
6502-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC404074
Subset
IM
Grants
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · CA16672 · United States
External Links
PubMed source DOI: 10.1073/pnas.0401711101 PMC Full Text View journal details
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