Early patterning and specification of cardiac progenitors in gastrulating mesoderm
W Patrick Devine,
Joshua D Wythe,
Matthew George,
Kazuko Koshiba-Takeuchi,
Benoit G Bruneau
Affiliations
W Patrick Devine
Gladstone Institute of Cardiovascular Disease, San Francisco, United States; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, United States; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States; Department of Pathology, University of California, San Francisco, San Francisco, United States
Joshua D Wythe
Gladstone Institute of Cardiovascular Disease, San Francisco, United States; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, United States
Matthew George
Gladstone Institute of Cardiovascular Disease, San Francisco, United States; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, United States; Developmental and Stem Cell Biology Program, University of San Francisco, San Francisco, United States
Kazuko Koshiba-Takeuchi
Gladstone Institute of Cardiovascular Disease, San Francisco, United States; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, United States
Benoit G Bruneau
Gladstone Institute of Cardiovascular Disease, San Francisco, United States; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, United States; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States; Developmental and Stem Cell Biology Program, University of San Francisco, San Francisco, United States
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.
