My lab uses nematode and stem cell models to investigate cell migration during nervous system development, with particular emphasis on the roles of heparan sulfate proteoglycans (HSPGs) and Eph receptor tyrosine kinases in this process.
C. elegans nematodes offer many advantages for investigating nervous system development. The animals are transparent, allowing the use of fluorescent labels to monitor cell movement and morphology. They have 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 investigation of gene function in this organism. We use time-lapse video microscopy and other techniques to understand how neuroblast migration contributes to C. elegans embryonic development. In addition, we are investigating how different HSPG core proteins contribute to axon branch formation.
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, with an emphasis on the role of EphR/ephrin function in cortical neurogenesis.