Fig. 9. A model for the promotion of ventricular myocardium proliferation by BMP signaling in neural crest derivatives. (A) A limited population of cells in a Wnt1-Cre lineage (blue) migrates to the epicardium, located between the pericardial wall and ventricular myocardium. (B) Within the epicardium, these cells transduce signals through BMPRIA, resulting in the production of a proliferative signal, both Bmpr1a dependent (solid arrows) and Bmpr1a independent (broken arrows), for the underlying ventricular myocardium. BMP ligands for BMPRIA are expressed in both the pericardium and ventricular myocardium. In mutant embryos (C), although BMPs and cells of the Wnt1-Cre lineage are both still present, BMPRIA is not present in Wnt1-Cre positive cells. This results in decreased production of the unidentified trophic factor downstream of BMPRIA, leading to decreased myocardial proliferation. (D) An alternative explanation for the myocardial proliferation defects involves the cardiac neural crest of the outflow tract (OFT). These cells may produce a long range signal (red arrows) stimulating proliferation throughout the myocardium. (E) In mutant embryos, decreased migration of NCCs into the OFT results in decreased production of myocardial proliferation signals.