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Related Experiment Video

Updated: Dec 21, 2025

Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
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Increased Tau Expression Correlates with Neuronal Maturation in the Developing Human Cerebral Cortex.

Kimberly L Fiock1, Martin E Smalley1, John F Crary2,3,4

  • 1Department of Pathology, University of Iowa, Iowa City, IA 52242.

Eneuro
|May 13, 2020
PubMed
Summary
This summary is machine-generated.

Tau expression increases with neuronal maturation in the developing brain. This study maps tau mRNA and protein in fetal brain development and iPSC organoids, identifying potential therapeutic targets for neurodegenerative and neurodevelopmental disorders.

Keywords:
Alzheimer’s diseasefetalneurodegenerationneurodevelopmentorganoidtau

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Tau protein is primarily known for its role in Alzheimer's disease (AD).
  • The expression patterns and cellular roles of tau during human brain development are not well understood.
  • Understanding early tau expression is crucial for neurodevelopmental and neurodegenerative disorders.

Purpose of the Study:

  • To map tau mRNA and protein expression at the cellular level in the developing human brain.
  • To investigate tau expression during fetal and neonatal periods.
  • To compare tau expression in the developing brain with induced pluripotent stem cell (iPSC)-derived cortical organoids.

Main Methods:

  • Single-cell RNA sequencing (sc-RNAseq) of developing human brain tissue.
  • RNA in situ hybridization (RNAscope) for precise mRNA localization.
  • Immunohistochemistry (IHC) and Western blotting for protein detection.
  • Analysis of sc-RNAseq and RNAscope data from iPSC-derived cortical organoids.

Main Results:

  • Tau mRNA expression begins in radial glia and significantly increases in maturing and mature neurons.
  • Low tau mRNA levels were observed in the subventricular zone (SVZ) and intermediate progenitors, with higher levels in more superficial neurons.
  • Tau protein expression was minimal in the germinal matrix and SVZ compared to more mature brain regions.
  • iPSC-derived cortical organoids exhibited similar tau expression patterns to the developing fetal brain.

Conclusions:

  • Tau expression progressively increases with neuronal maturation in the developing human brain.
  • The findings provide a cellular map of tau expression during early development.
  • This research lays the groundwork for investigating tau regulatory mechanisms and potential therapeutic targets for tauopathies and neurodevelopmental disorders.