Control of the differentiation potential of cardiac neural crest and impact on vascular performance

Abstract

sion, driven by a population of undifferentiated cells at the posterior-most end of the embryo, called the tailbud, that contributes cells to newly formed tissues of the body. This process of posterior growth requires the addition of new cells to multiple germ layers and tissue types. A long-standing debate has existed on whether cell types are specified during gastrulation andmaintained as lineage specific progenitor cells, or whether tailbud cells are multipotent stem cells that are specified to form tissue specific lineages by local signaling cues. Canonical Wnt signaling is present in the tailbud of all vertebrates throughout the duration of body formation, yet its role during posterior growth is unknown, hampered by the catastrophic disruption of posterior structures that occurs after traditional loss of function techniques. Using a combination of cell transplantation and heat-shock inducible Wnt inhibitor and activator transgenes in zebrafish, we show that canonical Wnt signaling plays multiple essential cell-autonomous roles in instructing the fate of tailbud stem cells. Wnt signaling is necessary and sufficient to specify mesoderm from a neural/ mesodermal precursor, and also functions within the mesodermal lineage to specify paraxial mesoderm instead of posterior vasculature. Our results demonstrate that multipotent stem cells persist within the tailbud throughout the formation of the vertebrate body, and that local Wnt signaling cues specify germ layer contribution and mesodermal tissue type specification to balance the allocation of tissues as the embryonic body extends.