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

Abstract

WW domain-containing transcription regulator 1 (TAZ) and Yes-associated protein (YAP) are transcriptional co-activators traditionally studied together as a part of the Hippo pathway and 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 the developing central nervous system, In this study, we show that TAZ regulates astrocytic differentiation and maturation of postnatal neural stem and progenitor cells (NPCs), and that TAZ mediates some but not all of the effects of bone morphogenetic protein (BMP) signaling on astrocytic development. By contrast, TAZ and YAP both mediate effects on NPC fate of {beta}1-integrin and integrin-linked kinase (ILK) signaling, and these effects are dependent on extracellular matrix (ECM) 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. Summary StatementAstrocytes are accounts for nearly half of the cells in the central nervous system, where they perform a diverse array of physiological functions. During development, astrocytes are primarily generated after neuronal differentiation in a stepwise manner from multiple glial committed progenitor subtypes. How gliogenic progenitors maintain proliferative properties versus differentiate into astrocytes is not fully understood. This work aims to elucidate how environmental signals utilizes molecularly similar intracellular components to achieve distinct developmental outcomes. In addition, many of the cell types that are involved in glial development are also present in brain tumors including glioblastoma. Knowledge on mechanisms regulating proliferation and differentiation of glial progenitors will provide insights into differences and similarities between normal and malignant cells.