scholarly journals Neural Progenitor Cells Undergoing Yap/Tead-Mediated Enhanced Self-Renewal Form Heterotopias More Easily in the Diencephalon than in the Telencephalon

2018 ◽  
Vol 43 (1) ◽  
pp. 180-189 ◽  
Author(s):  
Kanako Saito ◽  
Ryotaro Kawasoe ◽  
Hiroshi Sasaki ◽  
Ayano Kawaguchi ◽  
Takaki Miyata

Abstract Spatiotemporally ordered production of cells is essential for brain development. Normally, most undifferentiated neural progenitor cells (NPCs) face the apical (ventricular) surface of embryonic brain walls. Pathological detachment of NPCs from the apical surface and their invasion of outer neuronal territories, i.e., formation of NPC heterotopias, can disrupt the overall structure of the brain. Although NPC heterotopias have previously been observed in a variety of experimental contexts, the underlying mechanisms remain largely unknown. Yes-associated protein 1 (Yap1) and the TEA domain (Tead) proteins, which act downstream of Hippo signaling, enhance the stem-like characteristics of NPCs. Elevated expression of Yap1 or Tead in the neural tube (future spinal cord) induces massive NPC heterotopias, but Yap/Tead-induced expansion of NPCs in the developing brain has not been previously reported to produce NPC heterotopias. To determine whether NPC heterotopias occur in a regionally characteristic manner, we introduced the Yap1-S112A or Tead-VP16 into NPCs of the telencephalon and diencephalon, two neighboring but distinct forebrain regions, of embryonic day 10 mice by in utero electroporation, and compared NPC heterotopia formation. Although NPCs in both regions exhibited enhanced stem-like behaviors, heterotopias were larger and more frequent in the diencephalon than in the telencephalon. This result, the first example of Yap/Tead-induced NPC heterotopia in the forebrain, reveals that Yap/Tead-induced NPC heterotopia is not specific to the neural tube, and also suggests that this phenomenon depends on regional factors such as the three-dimensional geometry and assembly of these cells.

2021 ◽  
Author(s):  
Ziyun Jiang ◽  
Lingyan Yang ◽  
Linhong Zhou ◽  
Miao Xiao ◽  
Sancheng Ma ◽  
...  

Abstract Background: An early substantial loss of basal forebrain cholinergic neurons (BFCNs) is a common property of Alzheimer’s disease and the generation of functional BFCNs is related to learning and memory deficits. As a biocompatible and conductive scaffold for growth of neural stem cells, three-dimensional graphene foam (3D-GF) supports applications in tissue engineering and regenerative medicine. Although its effects on differentiation have been demonstrated, the effect of 3D-GF scaffold on the generation of BFCNs still remains unknown. Methods: In this study, we used 3D-GF as a culture substrate for neural progenitor cells (NPCs) and demonstrated that this scaffold material promotes the differentiation of BFCNs while maintaining excellent cell viability and proliferation. Results: Immunofluorescence analysis, RT-PCR, western blotting and ELISA revealed that the efficiency of BFCN differentiation on 3D-GF was significantly greater than that on tissue culture polystyrene substrates. Furthermore, a cell adhesion study suggested that 3D-GF scaffold enhances the expression of adhesion proteins including vinculin, integrin and N-cadherin. These findings indicate that 3D-GF scaffold materials are excellent candidates for the differentiation of BFCNs from NPCs. Conclusion: These results suggest new opportunities for the application of 3D-GF scaffold as a neural scaffold for Alzheimer’s disease therapies based on NPCs. Trial registration: Not applicable.


Author(s):  
Ayano Kawaguchi

During neocortical development, many neuronally differentiating cells (neurons and intermediate progenitor cells) are generated at the apical/ventricular surface by the division of neural progenitor cells (apical radial glial cells, aRGs). Neurogenic cell delamination, in which these neuronally differentiating cells retract their apical processes and depart from the apical surface, is the first step of their migration. Since the microenvironment established by the apical endfeet is crucial for maintaining neuroepithelial (NE)/aRGs, proper timing of the detachment of the apical endfeet is critical for the quantitative control of neurogenesis in cerebral development. During delamination, the microtubule–actin–AJ (adherens junction) configuration at the apical endfeet shows dynamic changes, concurrent with the constriction of the AJ ring at the apical endfeet and downregulation of cadherin expression. This process is mediated by transcriptional suppression of AJ-related molecules and multiple cascades to regulate cell adhesion and cytoskeletal architecture in a posttranscriptional manner. Recent advances have added molecules to the latter category: the interphase centrosome protein AKNA affects microtubule dynamics to destabilize the microtubule–actin–AJ complex, and the microtubule-associated protein Lzts1 inhibits microtubule assembly and activates actomyosin systems at the apical endfeet of differentiating cells. Moreover, Lzts1 induces the oblique division of aRGs, and loss of Lzts1 reduces the generation of outer radial glia (oRGs, also called basal radial glia, bRGs), another type of neural progenitor cell in the subventricular zone. These findings suggest that neurogenic cell delamination, and in some cases oRG generation, could be caused by a spectrum of interlinked mechanisms.


Epigenomics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1143-1161 ◽  
Author(s):  
Deepika Kandilya ◽  
Silambarasan Maskomani ◽  
Sukanya Shyamasundar ◽  
Paul Anantharajah Tambyah ◽  
Chan Shiao Yng ◽  
...  

Aim: This study was aimed to understand if Zika virus (ZIKV) alters the DNA methylome of human neural progenitor cells (hNPCs). Materials & methods: Whole genome DNA methylation profiling was performed using human methylationEPIC array in control and ZIKV infected hNPCs. Results & conclusion: ZIKV infection altered the DNA methylation of several genes such as WWTR1 (TAZ) and RASSF1 of Hippo signaling pathway which regulates organ size during brain development, and decreased the expression of several centrosomal-related microcephaly genes, and genes involved in stemness and differentiation in human neural progenitor cells. Overall, ZIKV downregulated the Hippo signaling pathway genes which perturb the stemness and differentiation process in hNPCs, which could form the basis for ZIKV-induced microcephaly.


2009 ◽  
Vol 30 (3) ◽  
pp. 653-662 ◽  
Author(s):  
Lian Li ◽  
Quan Jiang ◽  
Guangliang Ding ◽  
Li Zhang ◽  
Zheng Gang Zhang ◽  
...  

We tested the hypotheses that administration routes affect the migration and distribution of grafted neural progenitor cells (NPCs) in the ischemic brain and that the ischemic lesion plays a role in mediating the grafting process. Male Wistar rats ( n=41) were subjected to 2-h middle cerebral artery occlusion (MCAo), followed 1 day later by administration of magnetically labeled NPCs. Rats with MCAo were assigned to one of three treatment groups targeted for cell transplantation intra-arterially (IA), intracisternally (IC), or intravenously (IV). MRI measurements consisting of T2-weighted imaging and three-dimensional (3D) gradient echo imaging were performed 24 h after MCAo, 4 h after cell injection, and once a day for 4 days. Prussian blue staining was used to identify the labeled cells, 3D MRI to detect cell migration and distribution, and T2 map to assess lesion volumes. Intra-arterial (IA) administration showed significantly increased migration, a far more diffuse distribution pattern, and a larger number of transplanted NPCs in the target brain than IC or IV administration. However, high mortality with IA delivery (IA: 41%; IC: 17%; IV: 8%) poses a serious concern for using this route of administration. Animals with smaller lesions at the time of transplantation have fewer grafted cells in the parenchyma.


2004 ◽  
Vol 153 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Sankar Surendran ◽  
Lamya S. Shihabuddin ◽  
Jennifer Clarke ◽  
Tatyana V. Taksir ◽  
Gregory R. Stewart ◽  
...  

2003 ◽  
Vol 43 (16) ◽  
pp. 1699-1708 ◽  
Author(s):  
Hiroyuki Mizumoto ◽  
Keiko Mizumoto ◽  
Marie A Shatos ◽  
Henry Klassen ◽  
Michael J Young

Author(s):  
O. M. Tsupykov ◽  
T. A. Pivneva ◽  
A. O. Poddubna ◽  
V. M. Kyryk ◽  
O. V. Kuchuk ◽  
...  

2014 ◽  
Vol 2 (1) ◽  
pp. 85-89 ◽  
Author(s):  
O. Tsupykov ◽  
V. Kyryk ◽  
A. Mamchur ◽  
P. Poberezhnyi ◽  
G. Butenko ◽  
...  

The researchers have currently been actively investigating the possibilities for transplantation of the stem cells of various sources for treatment of the ischemic and degenerative diseases of the nervous systemInfluence of transplantation of the hippocampal neural progenitor cells (NPCs) on endogenous neurogenesis in the mice after brain ischemia-reperfusion induced by 20 min occlusion of both carotid arteries has been studied. Following 24 hours after occlusion the NPCsisolated from the hippocampus of the FVB-Cg-Tg(GFPU)5Nagy/J mice transgenic by the GFP gene were transplanted stereotactically into hippocampal CA1 area of the experimental animals. For evaluating neurogenesis in the hippocampus of the ischemic animals we used immunohistochemical staining of the brain slices for BrdU and doublecortin (DCX). It has been found that transplantation of neural progenitor cells increased the number of BrdU- and DCX-positive cells in the dentate gyrus of the hippocampus after short-term global ischemia.These data allow admit that NPC transplantation to the ischemic animals influences on endogenous adaptation processes in the brain and on the neurogenesis, in particular.


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