Fig. 8. Model for the molecular regulation of the boundaries within the cardio-craniofacial mesoderm in chick embryos. (A) At St. 8, the cardio-craniofacial mesoderm can be divided into CPM (blue), AHF/SpM (green) and differentiated SpM (red). (B) At St. 10, the division of the cardio-craniofacial mesoderm becomes more obvious. The AHF/SpM (green) is located underneath the pharynx, just dorsal to the heart. (C) At St. 18, both CPM and SpM contribute to BA1 and to the cardiac outflow tract. The distal part of BA1 mesoderm is SpM-derived (green) and is Isl1⁺, whereas the proximal region is CPM-derived (blue) and Myf5⁺. In the cardiac outflow tract, the contribution of the AHF/SpM is greater than that of the CPM, the contribution of which is seen in the more-distal part of the heart. (D) Heart formation is regulated by a combination of positive and negative signals from surrounding tissues. Whereas a signal(s) from the anterior endoderm works to promote heart formation in concert with BMP signals from the anterior lateral mesoderm, Wnt signals from the axial tissues (orange) repress heart formation in the CPM. (E) This study demonstrates that Wnt signaling can repress Isl1 and Nkx2.5 in the AHF/SpM, whereas treatment with Wnt antagonists (sFRP, purple) promotes Isl1 and Nkx2.5 expression. EP, electroporation; fg, foregut; nt, neural tube; da, dorsal aorta; n, notochord; h, heart; lm, lateral mesoderm; CPM, cranial paraxial mesoderm; AHF/SpM, anterior heart field/splanchnic mesoderm. Electron micrographs shown in A and B were reproduced with permission from Prof. Schoenwolf (University of Utah School of Medicine, Salt Lake City, UT).