What role do astroglial cells play in wiring the nervous system?

The adult brain is a highly complex structure capable of controlling every process in our body from the unconscious beating of our heart to the integration of all the sights, smells, and sounds in our environment for human reasoning. This remarkable diversity of function is all based on an elaborate circuitry of connected cells called neurons and their supportive glial cells. Neurons transmit electrical impulses throughout the body, and glial cells serve to support, connect, signal to, and insulate neural connections.

The precise wiring of the nervous system is all laid out during embryonic development. At the same time the brain architecture is first being organized, newly born neurons send out a long arm-like structure called an axon. The finger-like tip of the axon is motile and feels through the developing environment of the embryonic brain searching for its target. Target cells can be found at great distances away and even on the complete opposite side of the brain. Amazingly similar to how we navigate our automobiles to some destination, the axon's motile tip, known as the growth cone, searches for suitable roads, signs and traffic lights for direction. These traffic signals are displayed in the form of stationary or secreted proteins, to which an array of receptor proteins found on growth cones and migrating glial cells selectively interpret these guidance cues as either attractive or repulsive for axon growth. The axon crosses the road because there is a cue on the other side attracting it, and/or some cue behind it repelling it away. This is the process of axon guidance. Unfortunately, adult neurons are unable to recapitulate this dynamic growth and navigation, in part because the neuron may have lost its ability to sense the guidance cues and more importantly because the environment is no longer posting the necessary embryonic street signs. Understanding how the process of axon guidance is normally regulated during embryonic development will provide us key insights toward the creation of potential therapies for spinal cord injury and neurodegenerative diseases such as Parkinson's Disease, Alzheimer's Disease and Multiple Sclerosis.

The Barresi lab is focused on understanding how axons of Dopaminergic neurons (neurons lost in Parkinson's Disease) navigate from one hemisphere of the brain across the midline to the other hemisphere forming what is known as a commissure. Specifically we are 1) characterizing the glial cells at the midline that form a supportive growth substrate (road) for axons, 2) examining how astroglial cells and axons interact during development, 3) defining how the Roundabout family of receptors help both axons and glial cells interpret the environmental cues instructing where and whether these cell types will cross or be positioned at the midline. Lastly, 4) the Barresi Lab is also interested in the regulation of astroglial cell fate and the creation of Cancer models for the study of glial specific tumorogenesis. The Barresi Lab uses the Zebrafish (Danio rerio) as a model system to address all of these aspects of neural and glial cell development.

  Why Zebrafish?

  The zebrafish has recently become a favorite vertebrate model system to many researchers studying Neuroscience. Zebrafish can be bred in a small laboratory space and produce hundreds of embryos a day for analysis. Most importantly, zebrafish is the fastest developing vertebrate model system, going from a one-cell embryo to an embryo with a functioning nervous system in less than 24h. Additionally, zebrafish embryos are optically transparent, enabling the observation of single cell movement and tissue formation in living embryos. Experimentally, zebrafish provide the ability to use genetics, classical embryology, molecular biology, physiology, and pharmacology to answer our research questions.