My lab is interested in understanding how cell migration events contribute towards the development and function of the nervous system. Neurons often migrate long distances from their birthplace. In addition, neurons have to extend axons and dendrites over long distances towards their synaptic partners. Our goal is to identify the molecular cues that under pin these migrations, and to understand how these cues interact to govern nervous system development and function. In particular, we are interested in how heparan sulfate proteoglycans (HSPGs) and Eph receptor tyrosine kinases function during nervous system development. We employ two models to investigate neuronal cell migration events; (1) C. elegans neuroblast migration during embryonic development and (2) a mouse stem cell-to-forebrain neuronal differentiation.
C. elegans offers many advantages for investigating nervous system development. The animals are transparent, allowing the use of fluorescent labels to monitor cell movement and morphology. It has an invariant cell lineage so individual cells can be easily identified and monitored for developmental defects. Finally, well-developed genetic techniques and a fully sequenced genome facilitate the elucidation of gene function in this organism.
Stem cells offer great hope for personalized medicine and drug discovery. We have adopted a mouse stem cell-to-forebrain neural development model, originally developed by Austin Smith, to investigate cell migration during forebrain development. Mouse embryonic stem cells plated at low density undergo a default developmental program that recapitulates that seen during cortical layer specification of the mouse brain. We are using this model as a platform to identify genes required for cell migration during layer specification.