TAZ Represses the Neuronal Commitment of Neural Stem Cells

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Mechanisms regulating mammalian brain Neural Stem Progenitor Cells (NSPCs) quiescence, proliferation, and reprogramming remain unclear.
• The transcriptional co-factor TAZ, influenced by WNT and Hippo pathways, plays a role in NSPC homeostasis.

Purpose of the Study:

• To investigate the role of TAZ in NSPC homeostasis and neuronal differentiation.
• To elucidate the mechanistic function of TAZ in regulating neurogenesis.

Main Methods:

• Analysis of TAZ expression in murine neurogenic niches (striatal subventricular zone and dentate gyrus granular zone) and with aging.
• Utilized the midbrain-derived NSPC line ReNcell VM for mechanistic studies.
• Performed TAZ and TEADs knockdown and forced expression experiments in NSPCs.

Main Results:

• TAZ is highly expressed in NSPCs, declines with aging, and is lost in immature neurons.
• TAZ knockdown increased neuronal differentiation, while forced TAZ expression reduced it.
• TAZ/TEADs system represses SOX2 and proneuronal genes (ASCL1, NEUROG2, NEUROD1), impeding neurogenesis.

Conclusions:

• TAZ functions not only as a proliferation promoter but also as a repressor of neuronal differentiation in NSPCs.
• The TAZ/TEAD system is crucial for regulating NSPC fate decisions and neurogenesis.