| Development of the spinal cord is dependent on transforming a homogenous pool of undifferentiated spinal progenitors into units of cells with specific molecular profiles, morphology, and connectivity. The sheer number of events that must occur in a coordinated fashion makes understanding spinal cord development a difficult task. One particularly interesting element of spinal cord development is the intracellular responses by spinal progenitors that simultaneously receive multiple extracellular signals. How these signals translate into the generation of specific types of neurons is a well-studied field of developmental neurobiology but there are aspects that remain poorly understood or controversial.; This dissertation combines and extends knowledge in developmental biology, molecular biology, and biochemistry to enhance our understanding of spinal cord development. We investigate the biological and biochemical function of Tcf3, a transcriptional mediator of the Wnt/beta-catenin-signaling pathway. Then we explore the regulation and function of the Dbx progenitor domain, to better understand how this domain contributes to the formation of the spinal cord. Finally, we introduce a mutagenesis screen that seeks to identify tissue specific Wnt/beta-catenin signaling mutants to reveal novel functions and regulators of the canonical Wnt pathway.; The results of this research demonstrate that spinal cord development is highly dependent on the coordination of multiple extracellular signaling pathways in eliciting the appropriate intracellular response. Responses to these signals shape the identity, position, and function of the target cells. This dissertation also demonstrates a novel mechanism for conferring appropriate progenitor identity and progenitor state through Tcf3 as a transcriptional activator and repressor. Further, we show that aspects of expression, regulation, and function of the Dbx progenitor domain are conserved in zebrafish (Danio rerio). Also, because Dbx responds to a variety of extracellular signals in the intermediate spinal cord and because of its multipotency, this domain provides a unique area of the nervous system to study how these cues are integrated. The results of the mutagenesis screen shows that utilizing a GFP Wnt reporter line to identify tissue specific Wnt/beta-catenin mutants is useful. |
