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. 2022 Feb 23;603(7899):124–130. doi: 10.1038/s41586-022-04424-7

Fig. 3. UNC13A cryptic splicing is associated with loss of nuclear TDP-43 in patients with FTD and motor neuron disease.

Fig. 3

a, The design of the UNC13A e20/CE BaseScope probe targeting the alternatively spliced UNC13A transcript. Each Z binds to the transcript independently, and both must be in close proximity for successful signal amplification, ensuring binding specificity. b, BaseScope in situ hybridization using the UNC13A e20/CE probe, combined with immunofluorescence for TDP-43 and NeuN, was performed on sections from the medial frontal pole of patients with FTD and motor neuron disease (FTD–MND) and healthy controls. Representative images illustrate the presence of UNC13A CE (arrowheads) in neurons showing depletion of nuclear TDP-43. Neurons with normal nuclear TDP-43 in patients and controls show no CE signal (arrows). Images are maximum intensity projections of a confocal image z-stack. Scale bar, 10 µm. Images representative of six non-overlapping images from each individual. We optimized UNC13A probes on two cases and two controls in three separate experiments, with similar findings.