Our laboratory is interested in neural circuit assembly. To understand this complex problem, we are studying the development of a simple circuit formed, in part, by the connections between spinal motor neurons and limb muscles. We are using genetic and cellular manipulations in mouse and chick to address the following specific questions:
Spinal motor neuron axon guidanceWe have identified ephrin:Eph tyrosine kinase receptor signalling as a major effector of motor axon guidance. Our observations demonstrate that Netrin signalling also participates in motor axon guidance prompting us to address the question of how ephrin and Netrin signals are integrated in motor axon growth cones.
Neuronal migrationWe have recently shown that the Reelin signalling pathway is specifying the soma position of limb-innervating motor neurons within the ventral spinal cord. In the long term, we will address the question of whether aberrant motor neuron soma location affects motor circuit function.
Motor neuron survivalMotor neurons that innervate distinct muscles express specific combinations of neurotrophin receptors implying that motor neuron survival is controlled by combinatorial activity of neurotrophic survival factors. We are exploring this possibility by studying the expression of motor neuron survival factors in limb muscles and profiling motor neuron apoptosis in mouse mutants with altered limb patterning.
Electrical activity and neuronal developmentMotor neurons are electrically active even before they form synapses with their target muscles. We are exploring the role of this activity in the specification of motor neuron subtypes, the guidance of their axons and the assembly of motor circuits.
Development and function of the spinothalamic tractPain signals processed by neurons in the dorsal horn of the spinal cord are relayed to the sensory cortex through the thalamus. To gain insight into how nociceptive information is processed, we are studying the molecular basis for the formation of this important pathway using genetic approaches.