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The sensory nervous system is fundamental to our perception of our environment: it receives sensory information about the body in its current setting that it conveys to the central nervous system (CNS) for processing.  Our research focuses on the early development of sensory neurons and their connection with the CNS.  Elucidating this process is important for understanding normal nervous system development and for the coordination of repair. 

In the head, sensory neurons are born in neurogenic ectodermal placodes.  Neuroblasts migrate internally from the placodes to form the cranial sensory ganglia and ultimately establish stereotypical axonal connections with the CNS.  Incorrect control of neuroblast migration and axon path-finding will result in the failure to establish functional sensory circuits. 

I have demonstrated in chick that this control is mediated by the neural crest, a population of cells that migrate from the dorsal neural tube into the periphery.  Neuroblasts move inward along tracks of neural crest that extend from the hindbrain to the placode (see figure).  Functional analysis by surgical removal of the neural crest population results in the placodal neuroblasts remaining sub-ectodermal and sending out aberrant axonal projections, proving that there is an interaction between the two populations required for correct development.

Current Research Programme

We want to understand how these two different cell populations (neural crest cells and placodal neuroblasts) interact to enable the neuroblasts to migrate to the correct site for sensory ganglion formation. Little is currently know about neuronal migration in the peripheral nervous system (PNS), and this is a new role for neural crest.

Specific aims are:

Determine the cellular interactions between placodal neuroblasts and neural crest cells 

We are using In ovo electroporation to target fluorescent proteins to mark specific populations in the embryo.  It also opens up the possibility of using this system to look at the effect of specific molecules on migration and interaction of cells in embryos.

Identification of candidate molecules

To identify the molecular players involved in the cellular interaction we are using microarray analysis to compare the gene expression profile of placodal neuroblasts migrating on neural crest with that of placodal neuroblasts that are yet to leave the placode.  The aim is to find gene sets that are up- or down regulated in migrating neuroblasts on interaction with the neural crest.  Electroporation can then be used to assess gene function through over-expression, ectopic expression, and siRNA knock-down.  This will provide an easily accessible in vivo system to test the function of molecules implicated in neuronal migration and guidance.  

This research will provide a basis to address many questions in the future including:

Basic cell biology – how do neurons migrate?  Analysis both in vitro and in vivo: the placodal neuroblasts are more accessible than those buried within the developing CNS.

Developmental biology – molecular control and specificity of guidance mechanisms. 

Jo Begbie