Abstract

The dorsal horn of the spinal cord is responsible for integrating, processing and relaying sensory information from the external environment to other parts of the nervous system. During neural development six distinct populations of sensory interneurons, which process the sensory input from the periphery, arise in the dorsal spinal cord. The Bone Morphogenetic Proteins, which are expressed in the adjacent roof plate at the dorsal midline of the spinal cord, are both necessary and sufficient for the appropriate development of these cell types. However, the mode by which the BMPs specify each of these distinct dorsal IN populations has been unclear. The aim of this research is to illuminate the mechanism directing BMP signaling activity in the specification of neuronal identity in the developing dorsal spinal cord. In the scope of this work we have assessed the role of several components of the BMP signaling pathway, the different BMP ligands expressed in the spinal cord, the receptors that these ligands bind to and the downstream second messengers, the Smad proteins, that interpret these signals to regulate transcription. The goal of this work is to understand how the BMP signaling pathway directs neuronal identity and early circuit formation, both to better understand these processes in normal development and to inform future research aiming to co-opt these mechanisms for spinal repair.