(A) Modulators of tissue compliance applied during stages of early heart development exhibit defects, including pericardial and neural edemas (see arrows; scalebar, 1 mm), (B) altered AP length, and (C) increased rates of edema per clutch (N = 30–35 embryos over 4 clutches). (D) Compliance measured by microaspriation of HFR. (E) Compliance at stage 22 confirms blebbistatin and Y27632 increase and calyculin A decreases compliance (N = 11–17 embryos per treatment over 3 clutches). (F) Transverse sections through HFR at stage 28 show changes in polarity (aPKC or ZO-1) within progenitor population (red). Lower panels show the epithelial marker masked using tropomyosin expression (scale bar, 50 μm). (G) Apical intensity after small molecule inhibitor treatment (N = 9–13 embryos over 4 clutches). (H) Representative lateral confocal sections of stage 39 tadpole hearts (scale bar, 100 μm). (I) Cardiac anatomy after stage-specific inhibitor treatments as shown in Figure S2 (N = 5 embryos per treatment per period). Error bars represent mean ± SEM. * indicates p < 0.05; ** indicates p < 0.01. See also Figures S1, S2 and S3A.