Defining the role of primary cilia in shaping astrocyte development and response to brain insults
Astrocytes are a major type of cells that react to brain activity, injuries and diseases to help support optimal brain functions. It is increasingly recognized that astrocyte dysfunction is a leading cause of almost all major neurological disorders. These findings have stimulated excitements that astrocyte-based transplant cell therapy and drug discovery are emerging as promising therapeutic strategies for neurological disorders. However, to develop safe and effective treatments, there is an urgent need to address major gaps in our knowledge: How do astrocytes respond to the changes within their microenvironment in distinct physiological conditions? How do genetic and environmental factors induce astrocyte dysfunction? We recently made a novel discovery that astrocytes with defective primary cilia, small signaling antenna on astrocytes that detect external signals, show changes in shape, gene expression, and responses to invasive brain injury. Taking advantage of our unique ciliary experimental toolkit, in vivo live imaging, and single-cell RNAseq, we will test our hypothesis:
Hypothesis: Primary Cilia convey critical environmental signals to astrocytes to modulate astrocyte development and reactivation to brain insults.
Specifically, our goals are:
1. To define how ciliary activity modulates astrocytic activity in development and stab wound injury.
2. To define how primary cilia guide astrocyte differentiation and reaction to brain injury.
Jiami Guo , University of Calgary
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