Zebrafish Heart Regeneration Occurs by Cardiomyocyte

Dedifferentiation and ProliferationYajun Lin (Jocelyn)

Circulation Research August 4, 2006; 99 (3)

OutlineHeart Disease – heart failure

Heart Regeneration

Green Fluorescent Protein

Mechanistic Insight of Zebrafish Heart Regeneration

Heart Disease

CDC, National Vital Statistics System and the U.S. Census Bureau.

Heart Regeneration in Human

Mercader et al.European Society of Cardiology (2013)

Zebrafish Heart Regeneration

Auman et al. PLoS Biol.: 2007, 5(3);e53 PMID:17311471

Mechanistic Insight of Zebrafish Heart Regeneration

Research done by Jopling et al.

Barcelona, Spain.

PreparationTransgenic zebrafish were generated in which 4-

OHT-inducble Cre in under the control of the cardiomyocyte-specific cmlc2a promoter.

The reporter construct used the same cmlc2a promoter followed by a floxed stop cassette and enhanced green fluorescent protein.

Removal of the stop cassette by Cre allows the cmlc2a promoter within the transgene to drive the expression of GFP.

Green Fluorescent Protein

Regenerated cardiomyocytes are derived

from differentiated cardiomyocytes.

C Jopling et al. Nature 464, 606-609 (2010) doi:10.1038/nature08899

Differentiated cardiomyocytes re-enter the cell cycle.

C Jopling et al. Nature 464, 606-609 (2010) doi:10.1038/nature08899

Cardiomyocytes dedifferentiate, resulting in the disassembly of sarcomeric structure and

detachment.

C Jopling et al. Nature 464, 606-609 (2010) doi:10.1038/nature08899

plk1 is necessary for cardiac regeneration.

C Jopling et al. Nature 464, 606-609 (2010) doi:10.1038/nature08899

ConclusionZebrafish heart regeneration is driven primary by pre-

existing cardiomyocytes

The vest majority of heart muscle cell arise frim pre-existing cardiomyocytes

Pre-existing cardiomyocytes undergo limited dedifferentiation.

Cardiomyocytes close to the wound start to disassemble their sarcomeric structure, re-entering the cell cycle.

Many sarcomeric gene being downregulated after amputation.

References Heidi J Auman, Hope Coleman, Heather E Riley, Felix Olale, Huai-Jen Tsai, Deborah Yelon

Functional modulation of cardiac form through regionally confined cell shape changes. PLoS Biol.: 2007, 5(3);e53 PMID:17311471

Laflamme, Michael A, and Charles E Murry. 2011. "Heart regeneration." Nature 473, no. 7347: 326-335.

The 2006 Holiday Lectures Series "Potent Biology: Stem Cells, Cloning, and Regeneration.”

Jopling, Chris, Eduard Sleep, Marina Raya, Mercè Martí, Angel Raya, and Juan Carlos Izpisúa Belmonte. 2010. "Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation." Nature 464, no. 7288: 606-609.

O. Shimomura, FH Johnson, and Y Saiga (1962). Extraction, Purification and Properties of Aequorin, a Bioluminescent Protein from the Luminous Hydromedusan, Aequorea. J. Cellular and Comparative Physiol. 59: 223-239

Roger Heim, Andrew B. Cubitt & Roger Y. Tsien (1995) Improved Green Fluorescence. Nature. 373: 663-664.

The End