YAP and TAZ differentially regulate postnatal cortical progenitor proliferation and astrocyte differentiation

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• Yes-associated protein (YAP) and WW domain-containing transcription regulator 1 (TAZ) are key transcriptional co-activators in the Hippo pathway.
• These proteins are crucial for stem cell proliferation and differentiation, but can mediate distinct cellular outcomes.
• Their specific roles in neural stem and progenitor cell (NPC) differentiation remain incompletely understood.

Purpose of the Study:

• To elucidate the divergent functions of TAZ and YAP in mouse neural stem and progenitor cell (NPC) differentiation.
• To investigate the roles of TAZ and YAP in astrocytic differentiation and maturation.
• To determine the involvement of TAZ and YAP in signaling pathways regulating NPC fate, including bone morphogenetic protein (BMP) and integrin signaling.

Main Methods:

• Utilized mouse neural stem and progenitor cells (NPCs) to study TAZ and YAP functions.
• Investigated the effects of TAZ and YAP on astrocytic differentiation and maturation.
• Examined the mediation of BMP signaling and β1-integrin (ITGB1)/integrin-linked kinase signaling by TAZ and YAP.

Main Results:

• TAZ was found to regulate astrocytic differentiation and maturation, mediating some BMP signaling effects.
• Both TAZ and YAP were shown to mediate the effects of β1-integrin and integrin-linked kinase signaling on NPC fate.
• These integrin-mediated effects were dependent on extracellular matrix cues.

Conclusions:

• TAZ and YAP exhibit divergent functions in regulating astrocyte differentiation.
• YAP primarily regulates the cell cycle states of astrocytic progenitors.
• TAZ plays a critical role in the differentiation and maturation of astrocytic progenitors into mature astrocytes.