Our brain is composed of thousands of neuronal types interconnected with extraordinary specificity to form the neural circuits underlying normal nervous system function. Such neural circuits are a common feature of even the simplest nervous systems but how they are established still remains one of the key questions of developmental neurobiology. A remarkable example of neuronal organization are the somatotopic maps that preserve the contiguity between neuronal nuclei.

An important principle emerging from such maps is that cell body position and axon trajectory are tightly linked such that one can use the position of a neuron within the nervous system to predict the identity of its synaptic target. My laboratory is interested in how cell body position and axon trajectory are specified, and whether these two developmental processes are coordinated.

A simple organization is apparent in the arrangement of the cell bodies and axons of motor neurons of the lateral motor column (LMC) of the vertebrate spinal cord. The somatotopic organization of this system is evident in myotopy defined by the correlation between the position of motor neuron cell bodies and the position of their target muscles: motor neurons located within the medial LMC (LMCm) innervate ventral limb muscles, whereas motor neurons located within the lateral LMC (LMCl) innervate dorsal muscles.

LMC myotopy emerges through two binary developmental choices: after birth in the ventricular zone, (1) most LMC axons select either a dorsal or a ventral limb trajectory, as (2) LMC motor neuron cell bodies migrate either into a lateral or a medial position within the ventral spinal cord. The simple nature of this system makes it very attractive.


CURRENT OBJECTIVES:

Aim 1: Identify the effector molecules controlling LMC axonal projection. My studies have shown that the Lim1, Isl1 and Lmx1b LIM homeodomain transcription factors act in motor neurons and limb mesenchyme to control the trajectory of LMC motor axons. These transcription factorsmost likely influence LMC axonal projections by controlling theexpression of specific axon guidance cues and their receptors. Mylaboratory is currently studying the role of Eph tyrosine kinase receptors and their ephrin ligands as the effectors of LMC trajectory selection.

Aim 2: Identify the molecular mechanisms controling the mediolateral position of LMC cell bodies. Lim1 and Isl1 expression in LMC motor neurons also affects the position LMC motor neuron cell bodies within the spinal cord, suggesting that these transcription factors control the expression of effectors of cell migration. My laboratory is currently studing the role of Reelin signalling in this process.

Aim 3: Develop novel tools to study the specification of LMC somatotopy. To visualize the development of LMC motor neurons and their axonal projections in real time, my laboratory is currently developing imaging tools that will enable us to follow the development of LMC myotopy in in vitro cultures.