Enhanced Canonical Wnt Signaling During Early Zebrafish Development Perturbs the Interaction of Cardiac Mesoderm and Pharyngeal Endoderm and Causes Thyroid Specification Defects

Background: Congenital hypothyroidism due to thyroid dysgenesis is a frequent congenital endocrine disorder for which the molecular mechanisms remain unresolved in majority of cases. This situation reflects, part, our still limited knowledge about involved early steps specification from endoderm, particular extrinsic signaling cues that regulate foregut endoderm patterning. In this study, we used small molecules and genetic zebrafish models characterize role various pathways specification. Methods: We treated embryos during different developmental periods with small-molecule compounds known manipulate activity Wnt pathway observed effects thyroid, cardiovascular development using whole-mount situ hybridization transgenic fluorescent reporter models. antisense morpholino (MO) technique create acardiac model. For rescue experiments, bone morphogenetic protein (BMP) induction was obtained by manipulation heat-shock inducible lines. Results: Combined analyses revealed overactivation leads impaired concurrent severe defects cardiac When model MO-induced blockage cardiomyocyte differentiation, similar correlation observed, suggesting defective between mesoderm endodermal precursors contributes impairment. Rescue experiments through transient BMP could partially restore development. Conclusion: Collectively, results indicate critically required cell identify as likely source signals.