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Wnt/beta-catenin signaling promotes expansion of Isl-1-positive cardiac progenitor cells through regulation of FGF signaling.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2007 Jul; Vol. 117 (7), pp. 1794-804. - Publication Year :
- 2007
-
Abstract
- The anterior heart field (AHF), which contributes to the outflow tract and right ventricle of the heart, is defined in part by expression of the LIM homeobox transcription factor Isl-1. The importance of Isl-1-positive cells in cardiac development and homeostasis is underscored by the finding that these cells are required for cardiac development and act as cardiac stem/progenitor cells within the postnatal heart. However, the molecular pathways regulating these cells' expansion and differentiation are poorly understood. We show that Isl-1-positive AHF progenitor cells in mice were responsive to Wnt/beta-catenin signaling, and these responsive cells contributed to the outflow tract and right ventricle of the heart. Loss of Wnt/beta-catenin signaling in the AHF caused defective outflow tract and right ventricular development with a decrease in Isl-1-positive progenitors and loss of FGF signaling. Conversely, Wnt gain of function in these cells led to expansion of Isl-1-positive progenitors with a concomitant increase in FGF signaling through activation of a specific set of FGF ligands including FGF3, FGF10, FGF16, and FGF20. These data reveal what we believe to be a novel Wnt-FGF signaling axis required for expansion of Isl-1-positive AHF progenitors and suggest future therapies to increase the number and function of these cells for cardiac regeneration.
- Subjects :
- Animals
Basic Helix-Loop-Helix Transcription Factors metabolism
Cell Proliferation
Embryo, Mammalian cytology
Embryo, Mammalian embryology
Embryo, Mammalian metabolism
Gene Deletion
Gene Expression Regulation, Developmental
Genetic Markers
Heart embryology
Homeodomain Proteins genetics
LIM-Homeodomain Proteins
Mice
Transcription Factors
beta Catenin deficiency
beta Catenin genetics
Fibroblast Growth Factors metabolism
Homeodomain Proteins metabolism
Myoblasts, Cardiac cytology
Myoblasts, Cardiac metabolism
Signal Transduction
Wnt Proteins metabolism
beta Catenin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 117
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 17607356
- Full Text :
- https://doi.org/10.1172/JCI31731