Spatial and temporal mapping of 3R and 4R Tau isoforms during mouse brain development using BaseScope™ in situ hybridization technology

Microtubule-associated protein Tau (MAPT) is involved in the stability of microtubules, which maintain the cell shape. Tau protein is predominantly expressed in neurons, where it has a role in microtubule assembly and stability, axonal transport, and neurite outgrowth. In neurodegenerative diseases known as tauopathies, such as Alzheimer’s disease (AD), Tau function is compromised. Tau expression is developmentally regulated by alternative splicing, giving rise to 6 different isoforms in the human adult brain. Alternative splicing of exon 10 gives rise to protein isoforms with either three or four microtubule-binding repeats in the 3R Tau (exon 10 exclusion) and 4R Tau (exon 10 inclusion) splice variants, respectively. Expression of these isoforms is developmentally regulated and characterized by regionspecific neuroanatomic distribution. The high homology of these variants makes presents a challenge in distinguishing between these variants. In this study, we developed specialized probes that detect these variants with high specificity and sensitivity and further identify the spatio-temporal pattern of Tau variant expression during postnatal mouse brain development using our BaseScope technology.