Research in the Welshhans lab focuses on understanding how appropriate connectivity within the nervous system is established during development. We examine this process both in health and disease, with a focus on Down syndrome. We are interested in the mechanisms by which growth cones, which are the pathfinding structures of the developing neuron, migrate to and connect with their appropriate targets. The Welshhans lab employs a wide variety of molecular, cellular and advanced imaging techniques, including primary cell culture, viral-mediated gene expression, innovative fluorescent proteins and reporters, live cell imaging and TIRF microscopy, to elucidate the mechanisms underlying neural development. Proximately, the objective of this research is to understand how growth cone behavior is affected by external cues, as well as the intracellular molecular mechanisms that are activated by these cues. Ultimately, studying these mechanisms will allow us to understand how the early establishment of key neural circuits leads to the appropriate expression of adult cognition and behavior, as well as provide insight into treatments for neurodevelopmental disorders.
There are two major facets to our research program: (1) the neurodevelopmental basis of Down syndrome and (2) the molecular mechanisms regulating local translation of mRNAs during axon guidance.
Neurodevelopmental Basis of Down syndrome.
Down syndrome affects approximately 1 in every 700 infants, and is a major cause of a number of birth defects, including intellectual disability. Down syndrome results from the trisomy of human chromosome 21. However, hundreds of genes are located on this chromosome, and much is still unknown about the specific genes and molecular mechanisms contributing to the pathology of Down syndrome. Using both mouse and human models of Down syndrome, we investigate the molecular mechanisms underlying Down syndrome and how this contributes to the formation of inappropriate nervous system connectivity.
Molecular mechanisms regulating local translation of mRNAs during axon guidance.
The other major focus in the Welshhans lab examines the basic mechanisms underlying the transport and local translation of mRNAs in developing axons. Recently it has become evident that the local translation of select mRNA transcripts within the growth cone itself is necessary for cue-mediated axon growth and guidance. However, our understanding of which mRNAs contribute to appropriate axon guidance and the mechanisms underlying their translation is extremely limited. Research in my lab focuses on understanding the molecular and cellular mechanisms underlying local translation in growth cones, and how this regulates appropriate wiring of the developing nervous system.