scholarly journals The Wnt/ -catenin pathway directs neuronal differentiation of cortical neural precursor cells

Development ◽  
2004 ◽  
Vol 131 (12) ◽  
pp. 2791-2801 ◽  
Author(s):  
Y. Hirabayashi
PLoS ONE ◽  
2013 ◽  
Vol 8 (3) ◽  
pp. e57301 ◽  
Author(s):  
Ekaterina Novozhilova ◽  
Petri Olivius ◽  
Piyaporn Siratirakun ◽  
Cecilia Lundberg ◽  
Ulrica Englund-Johansson

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.


2011 ◽  
Vol 89 (9) ◽  
pp. 1388-1399 ◽  
Author(s):  
Masanori Gomi ◽  
Tomohiro Aoki ◽  
Yasushi Takagi ◽  
Masaki Nishimura ◽  
Yoshiyuki Ohsugi ◽  
...  

2008 ◽  
Vol 86 (9) ◽  
pp. 1936-1943 ◽  
Author(s):  
Makoto Ideguchi ◽  
Mizuya Shinoyama ◽  
Masanori Gomi ◽  
Hideki Hayashi ◽  
Nobuo Hashimoto ◽  
...  

2009 ◽  
Vol 7 (2) ◽  
pp. 85-96
Author(s):  
Joon-Ik Ahn ◽  
So-Young Kim ◽  
Moon-Jeong Ko ◽  
Hye-Joo Chung ◽  
Ho-Sang Jeong

2020 ◽  
Vol 29 (4) ◽  
pp. 235-248 ◽  
Author(s):  
Zhifu Wang ◽  
Yongtao Zheng ◽  
Mingzhe Zheng ◽  
Junjie Zhong ◽  
Fukai Ma ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Jiao ◽  
Björn Palmgren ◽  
Ekaterina Novozhilova ◽  
Ulrica Englund Johansson ◽  
Anne L. Spieles-Engemann ◽  
...  

Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation.Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application ofβ-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact.Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus.Conclusion. Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN).


2006 ◽  
Vol 80 (18) ◽  
pp. 8929-8939 ◽  
Author(s):  
Jenny Odeberg ◽  
Nina Wolmer ◽  
Scott Falci ◽  
Magnus Westgren ◽  
Åke Seiger ◽  
...  

ABSTRACT Human cytomegalovirus (HCMV) is the most common cause of congenital infections in developed countries, with an incidence varying between 0.5 and 2.2% and consequences varying from asymptomatic infection to lethal conditions for the fetus. Infants that are asymptomatic at birth may still develop neurological sequelae, such as hearing loss and mental retardation, at a later age. Infection of neural stem and precursor cells by HCMV and consequent disruption of the proliferation, differentiation, and/or migration of these cells may be the primary mechanism underlying the development of brain abnormalities. In the present investigation, we demonstrate that human neural precursor cells (NPCs) are permissive for HCMV infection, by both the laboratory strain Towne and the clinical isolate TB40, resulting in 55% and 72% inhibition of induced differentiation of human NPCs into neurons, respectively, when infection occurred at the onset of differentiation. This repression of neuronal differentiation required active viral replication and involved the expression of late HCMV gene products. This capacity of HCMV to prevent neuronal differentiation declined within 24 h after initiation of differentiation. Furthermore, the rate of cell proliferation in infected cultures was attenuated. Surprisingly, HCMV-infected cells exhibited an elevated frequency of apoptosis at 7 days following the onset of differentiation, at which time approximately 50% of the cells were apoptotic at a multiplicity of infection of 10. These findings indicate that HCMV has the capacity to reduce the ability of human NPCs to differentiate into neurons, which may offer one explanation for the abnormalities in brain development associated with congenital HCMV infection.


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