Collagen gel analysis of epithelial-mesenchymal transition in the embryo heart: An in vitro model system for the analysis of tissue interaction, signal transduction, and environmental effects

Alejandro Lencinas, André L P Tavares, Joey V. Barnett, Raymond B Runyan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The cellular process of epithelial-mesenchymal cell transition (EMT) is a critical event in development that is reiterated in adult pathologies of metastasis and organ fibrosis. An initial understanding of the cellular and molecular events of this process emerged from an in vitro examination of heart valve development. Explants of the chick atrioventricular valve-forming region were placed on collagen gels and removed to show that EMT was regulated by a tissue interaction. Subsequent studies showed that specific TGFβ isoforms and receptors were required and steps of activation and invasion could be distinguished. The assay was modified for mouse hearts and has been used to explore signal transduction and gene expression in both species. The principle advantages of the system are a defined temporal window, when EMT takes place and the ability to isolate cells at various stages of the EMT process. These advantages are largely unavailable in other developmental or adult models. As the mesenchymal cells produced by EMT in the heart are involved in defects found in congenital heart disease, there is also a direct relevance of cardiac EMT to human birth defects. This relationship has been explored in relation to environmental exposures and in a number of genetic models. This review provides both an overview of the findings developed from the assay and protocols to enable the use of the assay by other laboratories. The assay provides a versatile platform to explore roles of specific gene products, drugs, and environmental agents on a critical cellular process.

Original languageEnglish (US)
Pages (from-to)298-311
Number of pages14
JournalBirth Defects Research Part C - Embryo Today: Reviews
Volume93
Issue number4
DOIs
StatePublished - Dec 2011

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Epithelial-Mesenchymal Transition
Systems Analysis
Signal Transduction
Collagen
Embryonic Structures
Gels
Epithelial Cells
Genetic Models
Heart Valves
Environmental Exposure
In Vitro Techniques
Heart Diseases
Protein Isoforms
Fibrosis
Pathology
Neoplasm Metastasis
Gene Expression
Pharmaceutical Preparations
Genes

Keywords

  • Cell invasion
  • Collagen assay
  • EMT
  • Heart development
  • Invasion assay
  • Metastasis assay

ASJC Scopus subject areas

  • Embryology
  • Developmental Biology

Cite this

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abstract = "The cellular process of epithelial-mesenchymal cell transition (EMT) is a critical event in development that is reiterated in adult pathologies of metastasis and organ fibrosis. An initial understanding of the cellular and molecular events of this process emerged from an in vitro examination of heart valve development. Explants of the chick atrioventricular valve-forming region were placed on collagen gels and removed to show that EMT was regulated by a tissue interaction. Subsequent studies showed that specific TGFβ isoforms and receptors were required and steps of activation and invasion could be distinguished. The assay was modified for mouse hearts and has been used to explore signal transduction and gene expression in both species. The principle advantages of the system are a defined temporal window, when EMT takes place and the ability to isolate cells at various stages of the EMT process. These advantages are largely unavailable in other developmental or adult models. As the mesenchymal cells produced by EMT in the heart are involved in defects found in congenital heart disease, there is also a direct relevance of cardiac EMT to human birth defects. This relationship has been explored in relation to environmental exposures and in a number of genetic models. This review provides both an overview of the findings developed from the assay and protocols to enable the use of the assay by other laboratories. The assay provides a versatile platform to explore roles of specific gene products, drugs, and environmental agents on a critical cellular process.",
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