Inhibition of β-catenin dependent WNT signalling upregulates the transcriptional repressor NR0B1 and downregulates markers of an A9 phenotype in human embryonic stem cell-derived dopaminergic neurons: Implications for Parkinson's disease.

In this study we investigate how β-catenin-dependent WNT signalling impacts midbrain dopaminergic neuron (mDA) specification. mDA cultures at day 65 of differentiation responded to 25 days of the tankyrase inhibitor XAV969 (XAV, 100nM) with reduced expression of markers of an A9 mDA phenotype (KCNJ6, ALDH1A1 and TH) but increased expression of the transcriptional repressors NR0B1 and NR0B2. Overexpression of NR0B1 and or NR0B2 promoted a loss of A9 dopaminergic neuron phenotype markers (KCNJ6, ALDH1A1 and TH).

Compartmentalized microfluidic chambers enable long-term maintenance and communication between human pluripotent stem cell-derived forebrain and midbrain neurons.

Compartmentalized microfluidic devices are becoming increasingly popular and have proven to be valuable tools to probe neurobiological functions that are inherently difficult to study using traditional approaches. The ability of microfluidic devices to compartmentalize neurons offers considerable promise for disease modeling and drug discovery. Rodent cortical neurons/neural progenitors are commonly used in such studies but, while these cells mature rapidly, they do not possess the same receptors, ion channels and transport proteins found in human cortical neurons.