Fig. 5

Neuregulin signaling is required for the initiation of trabeculation. A–L: Confocal reconstructions of the ventricular myocardium in wild-type (wt) embryos expressing Tg(myl7:dsredt4) and Tg(myl7:egfp-hshras) and treated either with dimethyl sulfoxide (DMSO; A–C,G–I) or AG1478 (D–F,J–L). All reconstructions and sections are as shown in Figure 1, except that the atrioventricular (AV) canal is not visible in G and J. A white asterisk indicates area where the acquisition of fluorescent signal was blocked by overlying melanocytes. Yellow asterisks indicate examples of cells displaying epigenetic silencing of Tg(myl7:dsredt4). A–C: At 75 hours postfertilization (hpf), DMSO-treated embryos exhibit lumenal protrusions and primitive ridges (yellow arrowheads), similar to untreated wt embryos at a comparable stage (Fig. 2A–C). See also Supp. Movie S8. D–F: In contrast, AG1478-treated embryos do not initiate trabeculation and instead exhibit a smooth lumenal surface and a uniform thickness of the chamber wall at 75 hpf. See also Supp. Movie S9. G–I: At 99 hpf, DMSO-treated embryos exhibit normal ventricular morphology, including defined trabecular ridges (yellow arrowheads). See also Supp. Movie S10. J–L: In contrast, AG1478-treated embryos fail to form defined myocardial protrusions or ridges, although some subtle and variable displacements of lumenal cardiomyocytes do emerge (K, yellow arrowheads). See also Supp. Movie S11.