Bettina Schmid

Modeling neurodegeneration in zebrafish

PH 127

23.11.2018, 13:00

Most neurodegenerative diseases are characterized by aggregation of misfolded proteins.  Through aggregation, the proteins can contribute to disease by a loss of function mechanism. We use the zebrafish to investigate the physiological function of proteins associated with the neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal lobar dementia. Both diseases are pathologically characterized by the  aggregating protein TDP-43. We generated TDP-43 knock out zebrafish and identified muscle, neuronal and vascular phenotypes prior lethality.  In the vasculature, loss of TDP-43 leads to a severe mis-patterning due to loss of directed migration. We identified the integrina4/b1, fibronectin1 and VCAM1 pathway as a cause for the endothelial phenotype and are currently investigating its possible contribution to disease.