The ability of cells to detect and transduce mechanical stimuli is a fundamental biological process that underlies touch, pain and control of muscle tension. In vertebrates, a subpopulation of somatosensory neurons is specialized to detect these different mechanical stimuli but how they accomplish this task is at present not understood. Similarly, the developmental program that allows these neurons to differentiate into a diversity of cell types with very specific mechanosensitive traits is largely unknown.
We will employ a multidisciplinary approach geared towards the identification and characterization of molecules that are necessary for the development and function of mechanosensory neurons. Using the mouse as a model system, we will conduct a genetic screen that will allow us to isolate molecules such as transcription factors and signaling molecules involved in the differentiation of mechanosensory neurons. Subsequently, we will test their potential to drive differentiation of neuronal precursors into specific mechanosensory neurons using embryonic stem cell (ES-cell) technology. The resulting cell populations will be functionally analyzed for their mechanosensitive properties using live-cell imaging and electrophysiology and subsequently used to identify the underlying mechanosensory proteins.
This line of experiments will not only illuminate the genes necessary and sufficient for the generation of mechanosensitive neurons but will also allow the production of pure populations of sensory neurons, an invaluable tool for subsequent functional characterization of mechanosensory transduction that is currently impossible due to the heterogeneity of these cells in sensory ganglia in vivo.