The step by step differentiation of embryonic cells into different types of neurons lays the foundation for our sensory responses, motor commands, and cognitive behaviors. Our research explores this exquisite differentiation program in mammals using a combination of genetic and molecular biological methods. While the generation of such neural diversity is a complex process culminating in the most sophisticated of wiring circuits, one simplifying approach is to start by tracking the migration and differentiation paths taken by specific sets of cells originating from primitive neuroectoderm. Towards this goal, our lab has pioneered genetic tools to study progenitor-progeny cell relationships in the mouse. We are now applying these tools in full to study development of those brainstem neurons (nuclei) which provide the chief input to the cerebellum, and which collectively are called the precerebellar system.
In addition to studying neural development, we have initiated genetic experiments to uncover more general determinants of tissue pattern. Using insertional mutagenesis, we have created mutant mouse stocks that exhibit developmental defects ranging from skeletal abnormalities to hair and thymic defects. We are currently using large-insert DNA clones that span the transgene insertions to identify the affected genes. Through this approach, we have identified a BMP receptor that is the physiologic transducer mediating the development of digit cartilages. Transcriptional regulation of this gene has proven to be interesting and may represent a driving force in the evolution of distal limb form.