Epithelial to mesenchymal cell transformation (EMT) in the atrioventricular canal (AV canal) produces a population of fibroblast cells that contribute to the mitral and tricuspid valves of the fully formed heart. Formation of these cells is critical for normal heart development and disruption of this process leads to congenital heart disease. This study describes the role of the homeodomain containing transcription factor Mox-1 during this cell transformation process. Mox-1 protein and mRNA expression were detected during cell transformation in the cardiac cushions. This expression corresponded in time to stages of EMT characterized by cell shape change and invasion of the extracellular matrix. Antisense oligonucleotides to Mox-1 inhibited cell transformation in cultured AV canal explants. Previous reports indicated that the TGFβ3 signaling pathway also regulates cell transformation at similar stages. Experiments inhibiting the TGFβ3 pathway also inhibit Mox-1 expression. A 2kb portion of the Mox-1 promoter was cloned and a portion of this construct demonstrated a capacity to initiate transcription in AV canal cultures. The active fragment of the Mox-1 promoter was responsive to TGFβ3 signaling. This study indicates that Mox-1 is necessary but not sufficient for cell transformation in the AV canal cushions and is regulated by an important signaling pathway involved in this process.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/284125 |
| Date | January 2000 |
| Creators | Wendler, Christopher Charles |
| Contributors | Runyan, Raymond B. |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | en_US |
| Detected Language | English |
| Type | text, Dissertation-Reproduction (electronic) |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
Page generated in 0.0164 seconds