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

J Cell Sci. 2024 May 15;137(10):jcs261516. doi: 10.1242/jcs.261516. Epub 2024 May 20.

Abstract

WW domain-containing transcription regulator 1 (WWTR1, referred to here as TAZ) and Yes-associated protein (YAP, also known as YAP1) are transcriptional co-activators traditionally studied together as a part of the Hippo pathway, and are best known for their roles in stem cell proliferation and differentiation. Despite their similarities, TAZ and YAP can exert divergent cellular effects by differentially interacting with other signaling pathways that regulate stem cell maintenance or differentiation. In this study, we show in mouse neural stem and progenitor cells (NPCs) that TAZ regulates astrocytic differentiation and maturation, and that TAZ mediates some, but not all, of the effects of bone morphogenetic protein (BMP) signaling on astrocytic development. By contrast, both TAZ and YAP mediate the effects on NPC fate of β1-integrin (ITGB1) and integrin-linked kinase signaling, and these effects are dependent on extracellular matrix cues. These findings demonstrate that TAZ and YAP perform divergent functions in the regulation of astrocyte differentiation, where YAP regulates cell cycle states of astrocytic progenitors and TAZ regulates differentiation and maturation from astrocytic progenitors into astrocytes.

Keywords: Astrocytes; BMP; Integrins; Neural stem cells; TAZ; YAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Animals
  • Astrocytes* / cytology
  • Astrocytes* / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Differentiation*
  • Cell Proliferation*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Mice
  • Neural Stem Cells* / cytology
  • Neural Stem Cells* / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Protein Serine-Threonine Kinases
  • Signal Transduction*
  • Trans-Activators* / genetics
  • Trans-Activators* / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins* / metabolism
  • YAP-Signaling Proteins* / metabolism

Substances

  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Adaptor Proteins, Signal Transducing
  • Wwtr1 protein, mouse
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Trans-Activators
  • Phosphoproteins
  • Cell Cycle Proteins
  • Integrin beta1
  • integrin-linked kinase
  • Transcription Factors
  • Bone Morphogenetic Proteins
  • Protein Serine-Threonine Kinases

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