Retinoic acid production by endocardium and epicardium is an injury response essential for zebrafish heart regeneration.

Abstract:

: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.

journal_name

Dev Cell

journal_title

Developmental cell

authors

Kikuchi K,Holdway JE,Major RJ,Blum N,Dahn RD,Begemann G,Poss KD

doi

10.1016/j.devcel.2011.01.010

subject

Has Abstract

pub_date

2011-03-15 00:00:00

pages

397-404

issue

3

eissn

1534-5807

issn

1878-1551

pii

S1534-5807(11)00038-4

journal_volume

20

pub_type

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