The formation of precise topographic connections between motor neuron and their muscle targets critically depends on the pathfinding decisions made by axonal growth cones of each subtype of motor neuron during embryonic development. A general principle in motor circuit organization is the presence of distinctive transcriptional codes defining target specificity of each motor neuron subtype prior to innervation. We combine mouse genetics with biochemical and imaging approaches to address the molecular logic underlying motor neuron connectivity, with an emphasis on the interplay between genetic determinants of motor neuron development and signaling events operating at the growth cone during pathfinding.

 
E12.5 Mouse Spinal Cord Section
HB9:GFP-Green, EphA4-Red, Isl1-Blue

Although we focus on motor neurons as a model because of the powerful molecular and genetic tools available for these cells, our findings provide insights into the fundamental principles governing the wiring of the nervous system.

Our current areas of interest include:

  1. The identification of novel components of the signaling machineries controlling the sequential responsiveness of growth cones to attractive and repulsive cues
  2. The molecular basis of the unique capacity of motor neurons to project their axons to the periphery while maintaining their cell bodies within the nervous system
  3. The relationship between the dynamic organization of lipid-protein domains on the growth cone plasma membrane and the tuning of specific signaling modules at multiple choice points during axon pathfinding

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