During neural development, many cells navigate extensively to their final destinations where they form precise connections with their neighbors. We are interested in the molecules and mechanisms that guide cells in the developing nervous system to their targets, using chick, zebrafish and mouse as model systems. Specifically, we are focusing on the cues that guide and pattern motor neurons and neural crest cells.

Motor neurons, born in the forming central nervous system, extend their axons to innervate specific target muscles. Our previous studies indicated that chick motor neurons, their axons, and migratory pathways express unique combinations of Eph receptor tyrosine kinases (RTKs) and their ligands, the ephrins. Recently, we showed that distinct subsets of motor neurons that express EphA4 RTK respond differently to ephrin-A5. Our research focuses on unraveling the underlying mechanisms that account for these differential responses. Specifically, we have focused on the contribution of chick ephexin, a downstream signaling molecule that interacts directly with EphA4, to the distinct behaviors of EphA4-positive motor neurons. Using shRNA targeted specifically against c-ephexin, we showed that c-ephexin protein was required in LMC motor neurons for axon stalling at the base of the limb.

Neural crest cells, a stem cell-like population, emanate from the dorsal neural tube and migrate along stereotypical pathways to their target regions to form various derivatives in the peripheral nervous system including sensory/sympathetic ganglia, as well as components of the heart and craniofacial skeleton, and pigment cells. We are interested in how this stem cell population generates such a diverse array of derivatives. Furthermore, we are analyzing the molecules that guide neural crest movement and settling patterns. Using time-lapse imaging, in ovo electroporation, immunocytochemistry, and tissue culture paradigms, our goal is to define the cues that promote or inhibit cell migration and determine how they work at a mechanistic level.

Together, these studies will yield important insights about the positive and negative cues that generate precise patterns of cellular architecture during neural development. Furthermore, they should provide key data concerning the factors that control neural stem cell differentiation for the development of therapeutic strategies.

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