scholarly journals The MAP Kinase Phosphatase MKP-1 Modulates Neurogenesis via Effects on BNIP3 and Autophagy

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1871
Author(s):  
Yinghui Li ◽  
Marc W. Halterman

Inherited and acquired defects in neurogenesis contribute to neurodevelopmental disorders, dysfunctional neural plasticity, and may underlie pathology in a range of neurodegenerative conditions. Mitogen-activated protein kinases (MAPKs) regulate the proliferation, survival, and differentiation of neural stem cells. While the balance between MAPKs and the family of MAPK dual-specificity phosphatases (DUSPs) regulates axon branching and synaptic plasticity, the specific role that DUSPs play in neurogenesis remains unexplored. In the current study, we asked whether the canonical DUSP, MAP Kinase Phosphatase-1 (MKP-1), influences neural stem cell differentiation and the extent to which DUSP-dependent autophagy is operational in this context. Under basal conditions, Mkp-1 knockout mice generated fewer doublecortin (DCX) positive neurons within the dentate gyrus (DG) characterized by the accumulation of LC3 puncta. Analyses of wild-type neural stem cell (NSC) differentiation in vitro revealed increased Mkp-1 mRNA expression during the initial 24-h period. Notably, Mkp-1 KO NSC differentiation produced fewer Tuj1-positive neurons and was associated with increased expression of the BCL2/adenovirus E1B 19-kD protein-interacting protein 3 (BNIP3) and levels of autophagy. Conversely, Bnip3 knockdown in differentiated Mkp-1 KO NSCs reduced levels of autophagy and increased neuronal yields. These results indicate that MKP-1 exerts a pro-neurogenic bias during a critical window in NSC differentiation by regulating BNIP3 and basal autophagy levels.

2015 ◽  
Vol 3 (16) ◽  
pp. 3848-3859 ◽  
Author(s):  
Waleed Ahmed El-Said ◽  
Seung U. Kim ◽  
Jeong-Woo Choi

Neuro-cell chip was developed for non-invasive monitoring of neural stem cell stimulation using SERS technique that enabled the real-time monitoring, which is important for tissue development protocols.


PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e67411 ◽  
Author(s):  
Annalisa Lattanzi ◽  
Bernhard Gentner ◽  
Daniela Corno ◽  
Tiziano Di Tomaso ◽  
Pieter Mestdagh ◽  
...  

2012 ◽  
Vol 506 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Ji Hyun Park ◽  
Mi Ran Choi ◽  
Kyoung Sun Park ◽  
Seung Hyun Kim ◽  
Kyoung Hwa Jung ◽  
...  

Author(s):  
Peng Cui ◽  
Ping Zhang ◽  
Lin Yuan ◽  
Li Wang ◽  
Xin Guo ◽  
...  

Hypoxia-inducible factor 1α (HIF-1α) plays pivotal roles in maintaining pluripotency, and the developmental potential of pluripotent stem cells (PSCs). However, the mechanisms underlying HIF-1α regulation of neural stem cell (NSC) differentiation of human induced pluripotent stem cells (hiPSCs) remains unclear. In this study, we demonstrated that HIF-1α knockdown significantly inhibits the pluripotency and self-renewal potential of hiPSCs. We further uncovered that the disruption of HIF-1α promotes the NSC differentiation and development potential in vitro and in vivo. Mechanistically, HIF-1α knockdown significantly enhances mitofusin2 (MFN2)-mediated Wnt/β-catenin signaling, and excessive mitochondrial fusion could also promote the NSC differentiation potential of hiPSCs via activating the β-catenin signaling. Additionally, MFN2 significantly reverses the effects of HIF-1α overexpression on the NSC differentiation potential and β-catenin activity of hiPSCs. Furthermore, Wnt/β-catenin signaling inhibition could also reverse the effects of HIF-1α knockdown on the NSC differentiation potential of hiPSCs. This study provided a novel strategy for improving the directed differentiation efficiency of functional NSCs. These findings are important for the development of potential clinical interventions for neurological diseases caused by metabolic disorders.


Author(s):  
Ping Yuan ◽  
Lu Ding ◽  
Huili Chen ◽  
Yi Wang ◽  
Chunhong Li ◽  
...  

Exosomes, a key element of the central nervous system microenvironment, mediate intercellular communication via horizontally transferring bioactive molecules. Emerging evidence has implicated exosomes in the regulation of neurogenesis. Recently, we compared the neurogenic potential of exosomes released from primary mouse embryonic neural stem cells (NSCs) and astrocyte-reprogrammed NSCs, and observed diverse neurogenic potential of those two exosome populations in vitro. However, the roles of NSC-derived exosomes on NSC differentiation and the underlying mechanisms remain largely unknown. In this study, we firstly demonstrated that NSC-derived exosomes facilitate the differentiation of NSCs and the maturation of both neuronal and glial cells in defined conditions. We then identified miR-9, a pro-neural miRNA, as the most abundantly expressed miRNA in NSC-derived exosomes. The silencing of miR-9 in exosomes abrogates the positive effects of NSC-derived exosomes on the differentiation of NSCs. We further identified Hes1 as miR-9 downstream target, as the transfection of Hes1 siRNA restored the differentiation promoting potential of NSC-derived exosomes after knocking down exosomal miR-9. Thus, our data indicate that NSC-derived exosomes facilitate the differentiation of NSCs via transferring miR-9, which sheds light on the development of cell-free therapeutic strategies for treating neurodegeneration.


2009 ◽  
Vol 41 (4) ◽  
pp. 916-924 ◽  
Author(s):  
Le Su ◽  
Xin Lv ◽  
JiPing Xu ◽  
DeLing Yin ◽  
HaiYan Zhang ◽  
...  

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