Wnt11-Signaling Regulates Cardiac and Neural Crest Development

Abstract

This dissertation is composed of five major chapters. The first is a review of the literature discussing the secreted growth factor Wnt11 with particular interest in the Wnt11-dependent signaling cascades that regulate cell movements, followed by three chapters of research findings, and a final concluding chapter. Wnts are encoded by a family of 19 genes that play roles in development and disease. Homologs of Wnt11 are important regulators of cell movements in gastrulating embryos. In addition to gastrulation, Wnt11 genes show expression in other embryonic tissue including neural crest cells, the heart and the somite. Following the literature review, the first three chapters describe research that studies the roles of Wnt11-signaling during the development of the heart and neural crest. The first one demonstrates that Wnt11-signaling is required for heart morphogenesis. This work also refutes a proposed role for Wnt11 as a heart inducer. Next, the role of Wnt11 homologs is studied in the regulation of cranial and trunk neural crest cell migration. During neural crest development two Wnt genes are redundantly required to regulate cell migration Wnt11 and Wnt11-related (Wnt11-R). Trunk neural crest migration requires Wnt11-R for migration into the dorsal fin. Alternatively, cranial neural crest development predominantly requires Wnt11 while more severe migratory defects are observed when Wnt11 and Wnt11-R are co-inhibited. A final chapter discusses the overall conclusions about the general role that Wnt11 genes play during embryonic development.