Sorbs3 Modulates ErbB3 Signaling Required for Dorsal Root Ganglia Development

Abstract

The process of development, through which a single fertilized egg becomes a multicellular adult organism, is one of the most fascinating aspects of life. With intricate molecular guidance, thousands of specialized cell types arise from multipotent progenitors in spatiotemporal precision. In the first chapter of this dissertation, I review the processes that shape the development of one group of cells, the sensory neurons and glia that comprise the dorsal root ganglia. These cells types are derived from the multipotent and migratory neural crest. As such, the study of their development provides a beautiful model for understanding the coordination of the processes of migration and differentiation, common to many aspects of both development and disease progression. In the second chapter, I review how the ErbB receptor tyrosine kinases control several migratory processes in development. Sorbs3 is a scaffold protein that has been implicated in many aspects of cell migration and cell signaling; I review the processes shaped by this protein in the third chapter. In the fourth chapter, I present a study of the identification of a mutant lacking dorsal root ganglia neurons, and the identification of a role for Sorbs3 in mediating ErbB-dependent development of these neurons. Finally, I present implications of my work to development and disease, along with a discussion of open questions remaining in the field in the fifth chapter.