Communication between the left and right hemispheres of the brain requires precisely positioned neuronal cells with extensions called axons that span the midline of the organism. During embryogenesis these midline-crossing neurons are formed through an elaborate process of cell guidance that instructs pathfinding axons across the midline prior to reaching their synaptic targets. This process of "axon guidance" requires important cell-to-cell interactions between the pathfinding axon and the cells in its local environment. The Barresi Lab seeks to determine what the cell types are that make up the growth substrate for pathfinding axons, define the live interactions that occur, and determine whether a protein called Slit1a mediates these interactions at the midline.
The Barresi lab has characterized a simple system to assay midline-crossing axons interacting with a glial cells functioning as a growth substrate in the developing forebrains of living zebrafish zebrafish embryos. Using this system, they will also test the role Slit-Roundabout molecular signaling plays in regulating this interaction. They propose to exploit the embryological, molecular and genetic techniques available with the zebrafish model system to test directly whether glial cells play a role in midline crossing of these axons. Additionally, they will test whether Slit1a positively mediates axon-glial interactions. Barresi hypothesizes that distinct populations of astroglia are required for midline crossing through a Slit1a-Robo1 mediated mechanism of axon-glial interaction. This work will provide a molecular, cellular and behavioral understanding of how neuron-glial interactions occur in the live developing brain, which could change our current understanding of brain development that is mostly based on fixed tissue analysis.
Importantly, Barresi has also created a collaborative outreach program between an underserved public high school, a biotech company, and Smith College to train high school teachers and students in molecular and developmental biology. This effort is aimed to excite and prepare underrepresented students to consider and succeed in the pursuit of higher education in STEM related fields.
