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Development. 2018 Nov 21;145(22). pii: dev167510. doi: 10.1242/dev.167510.

Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development.

Gibb N1, Lazic S1,2, Yuan X1,3,2, Deshwar AR1,2, Leslie M1,3,2, Wilson MD3,2, Scott IC4,2,5,6.

Author information

1
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
2
Department of Molecular Genetics, University of Toronto, Ontario M5S 1A8, Canada.
3
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
4
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada ian.scott@sickkids.ca.
5
Ted Rogers Centre for Heart Research, Toronto, Ontario M5G 1M1, Canada.
6
Heart and Stroke Richard Lewar Centres of Excellence in Cardiovascular Research, Toronto, Ontario M5S 3H2, Canada.

Abstract

A key event in heart development is the timely addition of cardiac progenitor cells, defects in which can lead to congenital heart defects. However, how the balance and proportion of progenitor proliferation versus addition to the heart is regulated remains poorly understood. Here, we demonstrate that Hey2 functions to regulate the dynamics of cardiac progenitor addition to the zebrafish heart. We found that the previously noted increase in myocardial cell number found in the absence of Hey2 function was due to a pronounced expansion in the size of the cardiac progenitor pool. Expression analysis and lineage tracing of hey2-expressing cells showed that hey2 is active in cardiac progenitors. Hey2 acted to limit proliferation of cardiac progenitors, prior to heart tube formation. Use of a transplantation approach demonstrated a likely cell-autonomous (in cardiac progenitors) function for Hey2. Taken together, our data suggest a previously unappreciated role for Hey2 in controlling the proliferative capacity of cardiac progenitors, affecting the subsequent contribution of late-differentiating cardiac progenitors to the developing vertebrate heart.

KEYWORDS:

Cardiac progenitors; Heart development; Hey2; Second heart field; Zebrafish

PMID:
30355727
DOI:
10.1242/dev.167510
[Indexed for MEDLINE]
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