Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration.
Journal Article (Journal Article)
Zebrafish heart regeneration occurs through the activation of cardiomyocyte proliferation in areas of trauma. Here, we show that within 3 hr of ventricular injury, the entire endocardium undergoes morphological changes and induces expression of the retinoic acid (RA)-synthesizing enzyme raldh2. By one day posttrauma, raldh2 expression becomes localized to endocardial cells at the injury site, an area that is supplemented with raldh2-expressing epicardial cells as cardiogenesis begins. Induced transgenic inhibition of RA receptors or expression of an RA-degrading enzyme blocked regenerative cardiomyocyte proliferation. Injured hearts of the ancient fish Polypterus senegalus also induced and maintained robust endocardial and epicardial raldh2 expression coincident with cardiomyocyte proliferation, whereas poorly regenerative infarcted murine hearts did not. Our findings reveal that the endocardium is a dynamic, injury-responsive source of RA in zebrafish, and indicate key roles for endocardial and epicardial cells in targeting RA synthesis to damaged heart tissue and promoting cardiomyocyte proliferation.
Full Text
Duke Authors
Cited Authors
- Kikuchi, K; Holdway, JE; Major, RJ; Blum, N; Dahn, RD; Begemann, G; Poss, KD
Published Date
- March 15, 2011
Published In
Volume / Issue
- 20 / 3
Start / End Page
- 397 - 404
PubMed ID
- 21397850
Pubmed Central ID
- PMC3071981
Electronic International Standard Serial Number (EISSN)
- 1878-1551
Digital Object Identifier (DOI)
- 10.1016/j.devcel.2011.01.010
Language
- eng
Conference Location
- United States