Cell Shape and the Formation of Macro Cellular Assemblies During Embryo Development

The developing central nervous system is composed of many macrocellular assemblies of neurons that receive similar synaptic inputs and have similar axonal outputs. These so-called neuronal nuclei display a diverse set of shapes, ranging from ovoid and allantoid shapes to crescents and laminae. Over the past decade, we have shown that members of the cadherin family of cell adhesion molecules play roles critical to the formation of macro cellular assemblies of motor neurons in the brainstem and spinal cord. This cadherin expression is combinatorial in nature and drives specificity of cellular assembly, although the precise details of cadherin presentation within an individual cell and how this drives specificity are not known. Recently, we have found that a neuronal nucleus involved in sound source localization also utilizes cadherin function to form. However, this nucleus forms a lamina shape and some preliminary static modelling that we have performed suggests that the shape of the neurons in the nucleus drives formation of the lamina via cadherin function. This PhD project seeks to use mathematical models to understand how cell shape changes could influence formation of neuronal assemblies via adhesion mechanisms and to take the results of this modelling in vivo and in vitro to understand better how cadherin-based adhesion could drive the formation of different three dimensional shapes of neuronal nuclei. We shall focus the project initially on motor and auditory nuclei as well as the brainstem nuclei that process visual information, which form a nested curved layered structure. These experiments will be performed both in silico as well as in vivo in chicken and quail embryos and in reduced tissue culture experiments using either cell lines or primary populations of developing neurons. The techniques used include cell culture, in ovo electroporation, in situ hybridisation and immunofluorescence microscopy on thin tissue sections. There may also be an opportunity to do time-lapse imaging on thick sections of the cultured brainstem.