Ddx61-enriched condensates refine heart regeneration programs

Mira I. Pronobis, Sophia DeLuca, Siyun Lee, Lucas Garcia, Jianhong Ou, Nenad Bursac and Kenneth D. Poss ()
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Mira I. Pronobis: Duke University Medical Center
Sophia DeLuca: Duke University
Siyun Lee: Duke University Medical Center
Lucas Garcia: University of Denver
Jianhong Ou: Duke University Medical Center
Nenad Bursac: Duke University
Kenneth D. Poss: Duke University Medical Center

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract Gene regulatory mechanisms that underlie tissue regeneration have been largely studied at the level of transcription. Here, proximity labeling methods identify increased presence of the RNA helicase and P-body marker Ddx61 in adult zebrafish cardiomyocytes induced to divide by injury or mitogens. Ddx61 molecules form complex condensates in cardiomyocytes during cardiogenic settings in zebrafish, developing mice, and cultured human cells. ddx61 mutations disrupt cardiomyocyte proliferation and heart regeneration indices in adult zebrafish, and DDX6 knockdown reduces proliferation of cultured human cardiomyocytes. During heart regeneration, Ddx61 associates with and is required to restrain expression of mRNA encoding Chordin, a secreted BMP inhibitor that impedes regeneration if present at high levels. Our experiments indicate that mRNA sorting by context-dependent condensates can impact tissue regenerative capacity.

Date: 2025
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DOI: 10.1038/s41467-025-64026-5

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