Signaling Mechanisms Driving the Assembly of the Spinal Neuromuscular Circuitry

• Applicant: Professor Dr. Till Marquardt
• Subject Area: Developmental Biology
• Term: from 2007 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 40424281

Coordinate body movements depend on accurately wired nerve circuitries that connect motorand sensory neurons with the skeletal musculature. The central importance of these connections is illustrated by the debilitating consequences of diseases affecting motor neurons, such as Lou Gehrig’s disease (ALS), or post polio syndrome. Despite a wealth of available information on the differentiation and specification of distinct motor and sensory neuron types, little is known about how, during development, these cells become incorporated into functional nerve circuitries. My research generally aims at understanding how the precise connections of motor- and sensory neurons with the musculature are formed, and how they are ultimately assembled into the functional neuromuscular circuitry. This proposal more specifically addresses the role of interactions between cell-surface receptor proteins during two aspects of spinal neuromuscular circuit development in mouse and chick models: first, the coordination of motor and sensory projections during reflex circuit assembly (Aim 1); and second, the selective migration of different classes of motor axons towards their specific muscle targets (Aim 2). A third, independent project will furthermore aim at the identification and characterization of molecules involved in the functional specification of motor neurons (Aim 3). These studies take advantage of the clear topographic outline of neuromuscular connections that, together with a wealth of available cytological details, provides the invaluable advantage of allowing us to unanimously link neuron identity (and thus discrete gene expression profile) with specific axon targeting preference. Throughout this application we can take advantage of unique genetic and cytological tools for labeling, misexpressing and eliminating genes in different motor- and sensory neuron types. My previous research has lead to the development of novel in vitro assays that utilize these genetic tools to selectively study in detail genetically identified motor and sensory neuron projections in vitro and in vivo. I therefore feel we are uniquely positioned to address the biological questions raised by these aims, and to successfully conduct the studies in this proposal.

• DFG Programme: Independent Junior Research Groups