Cellular and molecular mechanisms of glial patterning and morphogenesis
Grantholders
Dr Ryan MacDonald
University College London, United Kingdom
Project summary
Glial cells provide the nervous system with critical physiological and homeostatic support. To carry out these supportive roles, glial cells must be properly positioned and shaped in the mature nervous system. The underlying developmental mechanisms are not well understood. Defects in glial cell morphology are associated with several neurodevelopmental and neurodegenerative diseases. My preliminary results, using time-lapse confocal imaging in the embryonic zebrafish retina, show that glial cells dynamically interact with their neighbouring cellular environment during development.
I will investigate how glial cells find their correct position and shape in the retina. I aim to characterise the specific glial-neuronal cell interactions and determine intrinsic molecular pathways regulating the distinct glial morphological responses. Combining confocal time-lapse imaging, cell specific transgenes and genetic ablation of specific neuron types I will investigate the nature and necessity of glial-neuronal interactions in real time in vivo. I will also use cell-labelling techniques to validate the glial specific expression of candidate genes identified in our previous transcriptomic dataset. The top three candidates will be selected for CRISPR-Cas9 mutagenesis.
This work will provide insight into the cellular and molecular mechanisms regulating of glial patterning and morphogenesis, aimed at uncovering the molecular regulators of dynamic cellular interactions.