Visualization of stochastic expression of clustered protocadherin β isoforms in vivo

The stochastic expression of clustered protocadherin (cPcdh) establishes a single-cell identity fundamental to cellular self/non-self-discrimination. However, it has been challenging to reveal the spatiotemporal patterning of the stochastic cPcdh expression in vivo . We developed XFP (tdTomato or GFP) knock-in mice using a new strategy to enhance XFP expression, which allows us to visualize cPcdhβ3 or 19-positive cells throughout the brain. These mouse lines demonstrate the cell-type selectivity, spatial biases, inter-individual differences, left-right asymmetry, developmental regulation, alteration in pathological or aging brain, and monoallelic expression of stochastic cPcdhβ expression in vivo . Our findings further demonstrate that the cPcdhβ3 expression undergoes significant changes in the mature brain over time. These results demonstrate the potential of these reporter mice to advance our understanding of cPcdh cellular barcode in vivo .