The branchiomeric skeletal muscles co-evolved with new chambers of the heart to enable predatory feeding in chordates. These co-evolved tissues develop from a common population in anterior splanchnic mesoderm, referred to as cardiopharyngeal mesoderm (CPM). The regulation and development of CPM are poorly understood. We describe an embryonic stem cell-based system in which MESP1 drives a PDGFRA+ population with dual cardiac and skeletal muscle differentiation potential, and gene expression resembling CPM. Using this system, we investigate the regulation of these bipotent progenitors, and find that cardiac specification is governed by an antagonistic TGFβ-BMP axis, while skeletal muscle specification is enhanced by Rho kinase inhibition. We define transcriptional signatures of the first committed CPM-derived cardiac and skeletal myogenic progenitors, and discover surface markers to distinguish cardiac (PODXL+) from the skeletal muscle (CDH4+) CPM derivatives. These tools open an accessible window on this developmentally and evolutionarily important population.
Bibliographical noteFunding Information:
This work was supported by the NIH (U01 HL100407 to M.K. and J.T.; P30 AR057220 pilot project award to S.S.K.C.). J.A. is an employee of Bio-Techne. We thank Cynthia DeKay for graphical design assistance and artwork. Received: August 28, 2015 Revised: December 2, 2015 Accepted: December 3, 2015 Published: January 12, 2016.
© 2016 The Authors.
Copyright 2017 Elsevier B.V., All rights reserved.
- cardiac development
- cardiopharyngeal mesoderm
- skeletal myogenesis