Cell shape and polarity during neurogenesis and brain morphogenesis

Jon Clarke

Professor of Anatomy

We want to understand how the brain and spinal cord is built in the vertebrate embryo. Who doesn’t? We use the relative simplicity and superior optical quality of the zebrafish embryo central nervous system to help understand some of the earliest and most fundamental steps in brain development. Our approach sits at the interface of cell biology and developmental neurobiology and uses advanced in vivo imaging and sub-cellular manipulations to understand how individual cell behaviours are regulated and integrated to build a working brain. Some of our current questions are: 1) Making the neuroepithelium; getting the scaffold right. The vertebrate CNS is derived from the epithelium of the embryo’s neural tube. Most of the important early events in neural development depend on the integrity of the apicobasal axis of this neuroepithelium, but how this polarity is generated and organised is not clear. We are investigating the role of extracellular matrix signalling, biophysical forces and the formation and remodelling of cell-cell junctions in neuroepithelial development. 2) Making neurons; right shape, right time, right place. How is cell polarity and shape remodelled to transform a newly born neuron at the apical surface of the neuroepithelium into a differentiating neuron with distinct axonal and dendritic projections at the basal surface? And what is the balance of intrinsic and extrinsic signals that determine neuron morphology? How is neuronal differentiation regulated in time and space to achieve the organised distribution of multiple neuron subtypes with appropriate spatial patterning?

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