Multiple Functions of Cerberus Cooperate to induce Heart downstream of Nodal

摘要: The TGFβ family member Nodal has been implicated in heart induction through misexpression of a dominant negative version the type I receptor (Alk4) and targeted deletion co-receptor Cripto murine ESCs mouse embryos; however, whether acts directly or indirectly to induce tissue interacts with other signaling molecules pathways remained unclear. Here we present Xenopus embryological studies demonstrating an unforeseen role for DAN protein Cerberus within presumptive foregut endoderm as essential differentiation cardiac mesoderm response Nodal. Ectopic activation non-cardiogenic ventroposterior mesendoderm, either by homologue XNr1 together constitutively active Alk4 (caAlk4), induced both markers Cerberus. Mosaic lineage tracing revealed that Nodal/Cripto caAlk4 cell non-autonomously, thus supporting idea another diffusible factor is mediator Nodal-induced cardiogenesis. alone was found sufficient initiate cardiogenesis at distance from its site synthesis. Conversely, morpholino-mediated specific knockdown reduced endogenous cardiomyogenesis ectopic resulting misactivation signaling. Since did not abrogate Wnt antagonist Dkk1, antagonists appear distinct pathways. This further supported combinatorial effect morpholino-medicated Hex, which required Dkk1-induced cardiogenesis, differential roles downstream effectors: pathway transcriptional repressor Hex while Dkk-1 These demonstrated depends on Nodal-mediated underlying endoderm, this functions parallel initiated antagonists. Both operate overlying mesoderm.