Overview

During development, the vertebrate nervous system self-assembles, starting from a single, fertilized egg.  The goal of our work is to understand how developmental-genetic programs guide this assembly process to give rise to the stereotyped and evolutionarily conserved architecture of the brain, allowing for its function.  We are particularly interested in cell-cell adhesion and cell-recognition molecules that help sculpt the three-dimensional structure of the brain and the formation of neural circuits.  Early in development, cell-cell interactions can coordinate the cell movements that sculpt the embryo.  Later, adhesion and cell contact can regulate the proliferation of progenitor cells and the production of neurons.  In addition, cell-recognition events can guide the outgrowth of axons and dendrites, the guidance of axons to their targets and the formation and stabilization of synaptic junctions.  It is essential to understand how each of these processes is regulated and how they are all integrated to generate the mature nervous system.  Mutations in many cell adhesion molecules can give rise to neurodevelopmental disorders, such as schizophrenia and autism spectrum disorders, yet it is not known how these mutations influence development to alter brain organization and function.  To address these questions, we use the zebrafish model system.  A small vertebrate, the zebrafish offers important advantages for the study of neural development.  First, the genomes are easy to modify, allowing us to make mutations in developmentally and clinically relevant genes.  Second, the embryos are small, transparent and develop rapidly, which enables visualization of brain development at high spatial and temporal resolution by time-lapse imaging.

To explore the role of cell adhesion in neural development, we focus on the development of the zebrafish visual system and the roles of both classical cadherins and protocadherins, which are families of homophilic cell adhesion molecules.

 

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