miR-17 regulates the proliferation and differentiation of the neural precursor cells during mouse corticogenesis

FEBS Journal ◽  
2014 ◽  
Vol 281 (4) ◽  
pp. 1144-1158 ◽  
Author(s):  
Susu Mao ◽  
Hanqin Li ◽  
Qi Sun ◽  
Ke Zen ◽  
Chen-Yu Zhang ◽  
...  
2009 ◽  
Vol 87 (7) ◽  
pp. 1522-1531 ◽  
Author(s):  
Meizhen Chen ◽  
Masumi Takano-Maruyama ◽  
Olivia M. Pereira-Smith ◽  
Gary O. Gaufo ◽  
Kaoru Tominaga

2008 ◽  
Vol 28 (24) ◽  
pp. 7427-7441 ◽  
Author(s):  
Takeshi Shimizu ◽  
Tetsushi Kagawa ◽  
Toshihiro Inoue ◽  
Aya Nonaka ◽  
Shinji Takada ◽  
...  

ABSTRACT The proliferation and differentiation of neural precursor cells are mutually exclusive during brain development. Despite its importance for precursor cell self renewal, the molecular linkage between these two events has remained unclear. Fibroblast growth factor 2 (FGF2) promotes neural precursor cell proliferation and concurrently inhibits their differentiation, suggesting a cross talk between proliferation and differentiation signaling pathways downstream of the FGF receptor. We demonstrate that FGF2 signaling through phosphatidylinositol 3 kinase activation inactivates glycogen synthase kinase 3β (GSK3β) and leads to the accumulation of β-catenin in a manner different from that in the Wnt canonical pathway. The nuclear accumulated β-catenin leads to cell proliferation by activating LEF/TCF transcription factors and concurrently inhibits neuronal differentiation by potentiating the Notch1-RBP-Jκ signaling pathway. β-Catenin and the Notch1 intracellular domain form a molecular complex with the promoter region of the antineurogenic hes1 gene, allowing its expression. This signaling interplay is especially essential for neural stem cell maintenance, since the misexpression of dominant-active GSK3β completely inhibits the self renewal of neurosphere-forming stem cells and prompts their neuronal differentiation. Thus, the GSK3β/β-catenin signaling axis regulated by FGF and Wnt signals plays a pivotal role in the maintenance of neural stem/precursor cells by linking the cell proliferation to the inhibition of differentiation.


Stem Cells ◽  
2010 ◽  
Vol 28 (10) ◽  
pp. 1816-1828 ◽  
Author(s):  
Yun Hee Kim ◽  
Jee-In Chung ◽  
Hyun Goo Woo ◽  
Yi-Sook Jung ◽  
Soo Hwan Lee ◽  
...  

Stem Cells ◽  
2008 ◽  
Vol 26 (7) ◽  
pp. 1796-1807 ◽  
Author(s):  
Lida Katsimpardi ◽  
Maria Gaitanou ◽  
Cecile E. Malnou ◽  
Pierre-Marie Lledo ◽  
Pierre Charneau ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Alexander Younsi ◽  
Guoli Zheng ◽  
Moritz Scherer ◽  
Lennart Riemann ◽  
Hao Zhang ◽  
...  

Stem cell therapy with neural precursor cells (NPCs) has the potential to improve neuroregeneration after spinal cord injury (SCI). Unfortunately, survival and differentiation of transplanted NPCs in the injured spinal cord remains low. Growth factors have been successfully used to improve NPC transplantation in animal models, but their extensive application is associated with a relevant financial burden and might hinder translation of findings into the clinical practice. In our current study, we assessed the potential of a reduced number of growth factors in different combinations and concentrations to increase proliferation and differentiation of NPCs in vitro. After identifying a “cocktail” (EGF, bFGF, and PDGF-AA) that directed cell fate towards the oligodendroglial and neuronal lineage while reducing astrocytic differentiation, we translated our findings into an in vivo model of cervical clip contusion/compression SCI at the C6 level in immunosuppressed Wistar rats, combining NPC transplantation and intrathecal administration of the growth factors 10 days after injury. Eight weeks after SCI, we could observe surviving NPCs in the injured animals that had mostly differentiated into oligodendrocytes and oligodendrocytic precursors. Moreover, “Stride length” and “Average Speed” in the CatWalk gait analysis were significantly improved 8 weeks after SCI, representing beneficial effects on the functional recovery with NPC transplantation and the administration of the three growth factors. Nevertheless, no effects on the BBB scores could be observed over the course of the experiment and regeneration of descending tracts as well as posttraumatic myelination remained unchanged. However, reactive astrogliosis, as well as posttraumatic inflammation and apoptosis was significantly reduced after NPC transplantation and GF administration. Our data suggest that NPC transplantation is feasible with the use of only EGF, bFGF, and PDGF-AA as supporting growth factors.


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