Zebrafishfollistatin-like 1bregulates cardiac contraction during early development

AbstractExtracellular glycoprotein Follistatin-like protein 1 (FSTL1) has been reported to be involved in multiple signaling pathways and biological processes during development and disease. In addition, some mouse studies have suggested an inhibitory role of FSTL1 in BMP signaling, in certain context. Yet, whether FSTL1 has biological functions in early heart development are largely unknown. In our functional studies, CRISPR/Cas9 genome editing was used to createfstl1aandfstl1binsertion/deletion mutations in zebrafish and our results suggest thatfstl1bis important in regulating heart development during early embryogenesis.in situhybridization revealed thatfstl1btranscripts are expressed in the developing zebrafish heart, andfstl1bhomozygous (-/-) mutant exhibited pericardial edema and showed significantly reduced contractility in the ventricle, with incomplete penetrance. We found that zebrafishfstl1b (-/-)mutant hearts formed a collapsed ventricle with strong reductions in the sarcomere structure protein alpha-actinin, although the number of cardiomyocytes was comparable to wild type control siblings. Further, normal levels offstl1bseems to prevent the expansion of Bmp signaling into ventricular myocytes, which is consistent with the previously established model of Bmp-dependent cardiac contraction. Together these results reveal the zebrafish orthologfstl1bregulates sarcomere structure and cardiac contractile function. In vertebrate developing heart, it might function as a key component in a novel pathway that constrains Bmp signaling from ventricular myocytes.