Early patterning and specification of cardiac progenitors in gastrulating mesoderm.

W Patrick Devine,Kazuko Koshiba-Takeuchi,Joshua D Wythe,Matthew George,Benoit G Bruneau

doi:10.7554/elife.03848

Abstract

Mammalian heart development requires precise allocation of cardiac progenitors. The existence of a multipotent progenitor for all anatomic and cellular components of the heart has been predicted but its identity and contribution to the two cardiac progenitor 'fields' has remained undefined. Here we show, using clonal genetic fate mapping, that Mesp1+ cells in gastrulating mesoderm are rapidly specified into committed cardiac precursors fated for distinct anatomic regions of the heart. We identify Smarcd3 as a marker of early specified cardiac precursors and identify within these precursors a compartment boundary at the future junction of the left and right ventricles that arises prior to morphogenesis. Our studies define the timing and hierarchy of cardiac progenitor specification and demonstrate that the cellular and anatomical fate of mesoderm-derived cardiac cells is specified very early. These findings will be important to understand the basis of congenital heart defects and to derive cardiac regeneration strategies.

Highlights

Mammalian heart development involves the allocation of cardiac progenitors in a discrete spatial and temporal order (Evans et al, 2010; Bruneau, 2013)
We performed in vivo clonal analysis by generating mosaic mice in which very few Mesp1+ cells were labeled at isolated clonal density via the mosaic analysis with double markers (MADM) system (Zong et al, 2005; Hippenmeyer et al, 2010) (Figure 1B–C)
We analyzed in fetuses (E12.5-E14.5) the anatomic distribution and cellular constituents of clones induced by Mesp1Cre (Saga et al, 1999)

Summary

Introduction

Mammalian heart development involves the allocation of cardiac progenitors in a discrete spatial and temporal order (Evans et al, 2010; Bruneau, 2013). Separation of the left and right ventricles is dependent on a single structure, the interventricular septum (IVS) and it has been postulated that the IVS myocardium has a dual contribution from these two heart fields (Bruneau et al, 1999; Takeuchi et al, 2003). The existence of these two cardiac progenitor ‘fields’ raises the question of when cardiac precursors are allocated to these populations and their contributions to mature structures in the heart, such as the IVS

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Results

Conclusion