Alexander disease patient astrocytes have impaired calcium wave propagation
Legend: A) Still images over time from mechanical stimulation of 6-month astrocytes loaded with Fluor-4AM and accompanying post-experiment GFAP stains. B) Average duration of increased calcium signal above threshold ± S.D. C) Average proportion of field of view traveled by calcium wave. D) Rate of calcium wave propagation induced by mechanical stimulation. E) Post-experiment cell quantification. For all n=10 per group. Scale bars = 100μm.
Citation: Jones JR et al., In preparation. 2017.
Abstract: Alexander disease (AxD) is caused by mutations in the astrocyte protein GFAP. Calcium wave propagation is a major component of astrocyte communication. Here we found that two different AxD causing mutations in GFAP resulted in calcium wave defects and that genetic correction of the mutation rescued the defect.
About the Lab: The Zhang laboratory intends to answer how functionally diversified neuronal and glial subtypes are born in the making of our human brain. They have developed models of neural differentiation from mouse, monkey, and human embryonic stem cells (ESCs) that recapitulate key events occurring during early embryo development, including induction of multipotential neuroepithelial cells that form neural tube-like structures, patterning of region-specific neural progenitors, and generation of neurons and glia with particular transmitter or functional phenotypes. In parallel, the lab is building transgenic human ESC lines with regulatable gene expression. The lab is dissecting biochemical interactions underlying the cellular differentiation processes under defined conditions. Such studies will hopefully bridge what they have learned from animal studies to human biology.