title: YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner.
abstract: Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)-dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development.
authors: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors: Dasol
authors: D
authors: Han
authors: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors: Sung-Hyun
authors: SH
authors: Byun
authors: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors: Soojeong
authors: S
authors: Park
authors: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors: Juwan
authors: J
authors: Kim
authors: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors: Inhee
authors: I
authors: Kim
authors: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors: Soobong
authors: S
authors: Ha
authors: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea.
authors: Mookwang
authors: M
authors: Kwon
authors: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, South Korea. Electronic address: keejung@skku.edu.
authors: Keejung
authors: K
authors: Yoon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000502:physiology; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C486310:Tead2 protein, mouse; C432156:Tead3 protein, mouse; C101204:Tead4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C517794:Wwtr1 protein, mouse; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse
keywords: Brain development; Neural stem cells; Tead; YAP/TAZ