Investigating the relationship between Sympathetic Nervous System Development and Neuroblastoma

Project Summary A common feature of embryonic development is that cells are born in one place and have to move as a cluster and regulate their differentiation before connecting with a vital target in a different location. One result of this dynamic morphogenetic event is assembly of the sympathetic nervous system that is essential for maintaining blood pressure, heart rate, and temperature control with improper development leading to birth defects and neuroblastoma cancer in infants. We are interested in understanding how the signals that regulate the collective cell movement and differentiation of the embryonic neural crest cells are orchestrated, spatially and temporally, to drive the emergence of the patterned sympathetic nervous system. To address this, we will implement an innovative combination of techniques from biological, in vivo imaging and single cell spatial transcriptomic sciences applied to the avian model system, most of which are not currently possible but may be translated to developing mammalian systems. This study will be significant because it will identify the signals involved in sympathetic nervous system development, linking the central and peripheral nervous systems -- with special focus on the role of TrkB and on determining the signals that mediate the migration, differentiation, survival, and molecular crosstalk between neural crest cells that ensure sympathetic nervous system circuit formation. The results of this study will provide critical information for surgical methods to correct by neural repair and mitigate the effects of sympathetic nervous system birth defects and translate into and inform improved drug design efforts targeting receptor tyrosine kinase signaling as a treatment for neuroblastoma and possible increase in infant survival.