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.
摘要：
含WW域的转录调节因子1（WWTR1，在此称为TAZ）和Yes相关蛋白（YAP，也称为YAP1）是传统上作为Hippo途径的一部分一起研究的转录共激活因子，并以其在干细胞增殖和分化中的作用而闻名。尽管他们有相似之处,TAZ和YAP可以通过与调节干细胞维持或分化的其他信号通路的差异相互作用来发挥不同的细胞效应。在这项研究中,我们在小鼠神经干细胞和祖细胞（NPCs）中显示TAZ调节星形细胞的分化和成熟，TAZ调解了一些，但不是全部,骨形态发生蛋白（BMP）信号对星形胶质细胞发育的影响。相比之下,TAZ和YAP均介导β1-整合素（ITGB1）和整合素连接激酶信号对NPC命运的影响，这些作用依赖于细胞外基质的线索。这些发现表明，TAZ和YAP在星形胶质细胞分化的调节中表现出不同的功能，其中YAP调节星形胶质细胞祖细胞的细胞周期状态，TAZ调节从星形胶质细胞祖细胞向星形胶质细胞的分化和成熟。
