The organization and function of the mature nervous system relies on the precision with which defined neuronal circuits are assembled into functional units during development. The aim of our studies is to understand the molecular and mechanistic basis involved in the establishment of specific connections within defined circuits of interconnected neurons. To address these questions, the main focus of our projects is on the molecular and cellular mechanisms controlling the specification of neuronal circuits in the developing vertebrate spinal cord. The spinal reflex circuit is perhaps the best-studied circuit in the context of what is known about the early steps of differentiation and about the established connectivity in the mature circuit. It therefore represents an ideal system to study molecular and cellular principles specifying selective connectivity between neuronal subtypes in vertebrates, which is ultimately of key importance to understand the function of neuronal networks.

The major focus of our research for the next several years will be on the establishment of connectivity in the spinal cord. Our previous work provides molecular and genetic entry points to approach questions of selective synaptic connectivity in the future. Future work will approach molecular and cellular events leading to specific connectivity from multiple different angles, aiming at pushing the analysis to the level of connectivity between defined functional units of the nervous system. These approaches have the common goal to identify principles governing the establishment of connectivity at the level of single neurons and their synapses in a defined vertebrate neuronal circuit during development. In the longer term, we hope to expand our acquired knowledge to neuronal circuits interconnected with spinal circuitry. To unravel the molecular cascades of genes controlling neuronal circuit formation, we combine techniques such as gain- and loss-of-function mouse genetics, light microscope imaging of fluorescently labeled neuronal subpopulations, electrophysiological analysis and gene expression profiling.