YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner
| Autor: | Inhee Kim, Dasol Han, Soojeong Park, Keejung Yoon, Sung-Hyun Byun, Soobong Ha, Juwan Kim, Mookwang Kwon |
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| Rok vydání: | 2015 |
| Předmět: |
Molecular Sequence Data
Cell Biophysics Muscle Proteins Cell Cycle Proteins Mice Inbred Strains Biology Biochemistry SOX2 Pregnancy Neurosphere medicine Animals TEAD2 Molecular Biology Embryonic Stem Cells Adaptor Proteins Signal Transducing Neurons Base Sequence Cell growth Brain Gene Expression Regulation Developmental TEA Domain Transcription Factors YAP-Signaling Proteins Cell Biology Embryo Mammalian Phosphoproteins Embryonic stem cell Neural stem cell Cell biology DNA-Binding Proteins medicine.anatomical_structure Trans-Activators Female Stem cell Signal Transduction Transcription Factors |
| Zdroj: | Biochemical and Biophysical Research Communications. 458:110-116 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2015.01.077 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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