Cody J. Smith Elizabeth and Michael Gallagher Assistant Professor

Neural Development and Regeneration
Cody J. Smith

Research Interests:

The Smith Lab studies how to build the nervous system during development and regeneration. There is a significant gap in our understanding of how the precise organization of neural cells, specifically glia, functionally impacts the ability for animals to sense, react and learn. To address this I am interested in understanding how distinct glial and neuronal cell-types from both the CNS and PNS work in concert to build and organize the nervous system. During development and regeneration, these discrete neural cells often originate from different progenitors, migrate long distances, interact, integrate and differentiate, all in a choreographed manner. By examining these cells in developmental and regeneration contexts, the goal of the lab is to gain insight into not only how functional circuits are created, maintained and change during development but also into how both glia and neurons impact regeneration following injury, neurodevelopmental disorders such as Charcot Marie Tooth Disorder (CMT), and neurodegenerative diseases like Multiple Sclerosis (MS).

As a model to better understand how discrete cell-types work together to build/rebuild the nervous system our goal is to initially focus on regions in the nervous system where glial and neuronal cell-types from both the CNS and PNS must coordinate their migration, differentiation and maintenance. The precise assembly of these CNS/PNS interfaces creates a directional flow of information with sensory information entering the CNS and motor information leaving to the periphery. By investigating these areas of the nervous system we can ask questions such as:

  • What organizational principles build/re-build selective cellular boundaries? Axons travel uninterrupted through these interfaces but most glial cells that are essential for aiding these axons cannot. Interestingly, little is known about how axons are permitted to traverse these transition zones while cell bodies of neurons and glia typically do not. We are investigating the cellular and molecular determinants of this phenomenon with the hope to provide insight into defects in cellular restriction in disease.
  • How do axons and glia communicate and coordinate to establish functional circuits? How glial and neuronal populations assemble at specific regions of the nervous system is also poorly understood. However, both CNS and PNS glial cell-types must interact and coordinate their differentiation and maturation as the axons do the same. By investigating the developmental blueprint for assembling nervous system regions we hope to provide insight into how regeneration of nerves either succeeds or fails.

My approach is to use time-lapse imaging of live zebrafish in combination with molecular and genetic tools. The advantage of this system is the ability to image neural cells migrate, proliferate and interact in a live animal over an extended period of time. We are now also using these imaging techniques to visualize cytosolic components in the cells as they build/rebuild the nervous system. We compliment these imaging techniques with molecular biology and genetic techniques, such as the CRISPR system, to reveal previously unknown molecular mechanisms. In the short term, these genetic strategies in zebrafish will reveal candidate molecules that impact the precise organization and regeneration of neural cells, specifically glia. However, the plan is to use a similar project outline to study other aspects of neural development and regeneration, utilizing time-lapse imaging to characterize a phenomenon and then molecular techniques to reveal unknown determinants and their potential impact on disease.

 

Biography:

  • Alfred P. Sloan Fellow of Neuroscience 2017
  • Elizabeth and Michael Gallagher Assistant Professor, Department of Biological Sciences, Center for Stem Cells and Regenerative Medicine 2016-Present
  • Postdoctoral Fellow, Department of Biology, University of Virginia, Charlottesville VA 2012-2016
  • Chair, Gordon Research Seminar, Dendrites, Ventura CA 2015
  • Graduate Student, Cell and Developmental Biology Department, Vanderbilt University, Nashville TN 2007-2012
  • Assistant Chair, Gordon Research Seminar, Dendrites, Switzerland 2013
  • PhD, Cell and Developmental Biology, Vanderbilt University 2012
  • B.S., Biology, Mercyhurst University 2007

 

Recent Papers:

  • Smith, Cody J., Kimberly Johnson, Taylor G. Welsh, Michael Barresi, and Sarah Kucenas. Radial glia inhibit peripheral glial infiltration into the spinal cord at the spinal motor exit point. Glia. 2016
  • Kimberly Johnson, Jessica Barragan, Sarah Bashiruddin, Cody J. Smith, Chelsea Tyrrell, Michael J. Parsons, Rosemarie Doris, Sarah Kucenas, Gerald B. Downes, Carla Velez, Catalina Sakai, Narendra Pathak, Katrina Anderson, Rachael Stein, Stephen H. Devoto, Jeff S. Mumm and Michael J.F. Barresi. Gfap-positive radial glial cells are an essential progenitor population for later born neurons and glia in the zebrafish spinal cord. Glia. 2016
  • Wheeler, Michael A., Cody J Smith, Matteo Ottolini, Bryan S Barker, Aarti M Purohit, Ryan M Grippo, Ronald P Gaykema, Anthony J Spano, Mark P Beenhakker, Sarah Kucenas, Manoj K Patel, Christopher D Deppmann & Ali D Güler. Genetically Magnetic Control of the Nervous System. Nature Neuroscience. 2016
  • Smith, Cody J., Angela Morris, Taylor Garrett, and Sarah Kucenas. Contact-Mediated Inhibition Between Oligodendrocyte Progenitor Cells and Motor Exit Point Glia Establish the Spinal Cord Transition Zone. PLoS Biology. 2014. PMID: 25268888.
  • Smith, Cody J., Tim D. Obrien, Marios Chatzigeorgiou, Clay Spencer, Lani Feingold-Link, William R Schafer, David M. Miller. Sensory neuron fates are distinguished by a transcriptional switch that regulates dendrite branch stabilization. Neuron 2013. PMID: 23889932.
  • Smith, Cody J., Joseph D. Watson, Miri K. Vanhoven, Daniel A. Colon-Ramos and David M. Miller III. Netrin (UNC-6) mediates dendritic self-avoidance. Nature Neuroscience 2012. PMID: 22426253