Temporally Distinct Six2-Positive Second Heart Field Progenitors Regulate Mammalian Heart Development and Disease

Publication date: 24 January 2017
Source:Cell Reports, Volume 18, Issue 4
Author(s): Zhengfang Zhou, Jingying Wang, Chaoshe Guo, Weiting Chang, Jian Zhuang, Ping Zhu, Xue Li
The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors. Six2-positive (Six2⁺) progenitors are rapidly recruited and assigned, and their descendants are allocated successively to regions of the heart from the right ventricle (RV) to the pulmonary trunk. Global ablation of Six2⁺ progenitors resulted in RV hypoplasia and pulmonary atresia. An early stage-specific ablation of a small subset of Six2⁺ progenitors did not cause any apparent structural defect at birth but rather resulted in adult-onset cardiac hypertrophy and dysfunction. Furthermore, Six2 expression depends in part on Shh signaling, and Shh deletion resulted in severe deficiency of Six2⁺ progenitors. Collectively, these findings unveil the chronological features of cardiogenesis, in which the mammalian heart is built sequentially by temporally distinct populations of cardiac progenitors, and provide insights into late-onset congenital heart disease.

Graphical abstract

Teaser

The process of building multiple components of the mammalian heart remains poorly understood. Zhou et al. identify and characterize a population of temporally distinct Six2-positive cardiac progenitors and suggest that the heart is made progressively by adding new components to the preexisting structures.


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