Fig 6. Restoration of Nipbl expression in different heart lineages rescues heart defects.

MRI analysis of E17.5 hearts show that Nipbl^FLEX/+ mice exhibit ASDs at a frequency of ~30% (yellow arrowheads in A–C, and D). The incidence of heart defects was significantly reduced in mice in which Nipbl was restored in all tissues (Nipbl^FLEX/+;Nanog-Cre), specifically in the cTnt domain (Nipbl^FLEX/+;cTnt-Cre), or specifically in the Sox17 domain (Nipbl^FLEX/+;Sox17-2A-iCre) (D, asterisks: Chi-square, p < 0.05). Chi-square analysis on the incidence of heart defects between the three rescued lines indicated no significant difference from one another (Chi-square, p > 0.71). Progeny are on various backgrounds depending on parental backgrounds: Nipbl^FLEX/+ (mixed), wildtype (CD-1), cTnt-Cre (CD-1), Nanog-Cre (C57Bl6/J), and Sox17-2A-iCre (C57Bl6/J); the incidence of heart defects in Nipbl^FLEX/+ embryos from each of these crosses did not differ significantly (p > 0.89 by Chi-square analysis; S1 Data). Size bar = 500 μm. lv, left ventricle; rv, right ventricle