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Beta catenin and neural progenitors

Navid Nouri, Meera J Patel, Milan Joksimovic, Jean-Francois Poulin, Angela Anderegg, M Mark Taketo, Yong-Chao Ma, Rajeshwar Awatramani
The floor plate (FP), a ventral midline structure of the developing neural tube, has differential neurogenic capabilities along the anterior-posterior axis. The midbrain FP, unlike the hindbrain and spinal cord floor plate, is highly neurogenic and produces midbrain dopaminergic (mDA) neurons. Canonical Wnt/beta-catenin signaling, at least in part, is thought to account for the difference in neurogenic capability. Removal of beta-catenin results in mDA progenitor specification defects as well as a profound reduction of neurogenesis...
September 2015: Molecular and Cellular Neurosciences
Fiete Haack, Heiko Lemcke, Roland Ewald, Tareck Rharass, Adelinde M Uhrmacher
Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation...
March 2015: PLoS Computational Biology
Wen Luo, Xia Zhao, Hengwei Jin, Lichan Tao, Jingai Zhu, Huijuan Wang, Brian A Hemmings, Zhongzhou Yang
Second heart field (SHF) progenitors exhibit continued proliferation and delayed differentiation, which are modulated by FGF4/8/10, BMP and canonical Wnt/β-catenin signaling. PTEN-Akt signaling regulates the stem cell/progenitor cell homeostasis in several systems, such as hematopoietic stem cells, intestinal stem cells and neural progenitor cells. To address whether PTEN-Akt signaling is involved in regulating cardiac progenitors, we deleted Pten in SHF progenitors. Deletion of Pten caused SHF expansion and increased the size of the SHF derivatives, the right ventricle and the outflow tract...
February 15, 2015: Development
Whitney E Heavner, Cynthia L Andoniadou, Larysa H Pevny
BACKGROUND: Eye development in vertebrates relies on the critical regulation of SOX2 expression. Humans with mutations in SOX2 often suffer from eye defects including anophthalmia (no eye) and microphthalmia (small eye). In mice, deletion of Sox2 in optic cup progenitor cells results in loss of neural competence and cell fate conversion of the neural retina to a non-neurogenic fate, specifically the acquisition of fate associated with progenitors of the ciliary epithelium. This fate is also promoted with constitutive expression of stabilized β-Catenin in the optic cup, where the WNT pathway is up-regulated...
2014: Neural Development
Siwei Zhang, Jingjing Li, Robert Lea, Kris Vleminckx, Enrique Amaya
Brain regionalisation, neuronal subtype diversification and circuit connectivity are crucial events in the establishment of higher cognitive functions. Here we report the requirement for the transcriptional repressor Fezf2 for proper differentiation of neural progenitor cells during the development of the Xenopus forebrain. Depletion of Fezf2 induces apoptosis in postmitotic neural progenitors, with concomitant reduction in forebrain size and neuronal differentiation. Mechanistically, we found that Fezf2 stimulates neuronal differentiation by promoting Wnt/β-catenin signalling in the developing forebrain...
December 2014: Development
Arnon Dias Jurberg, Rita Aires, Ana Nóvoa, Jennifer Elizabeth Rowland, Moisés Mallo
Extension of the vertebrate body results from the concerted activity of many signals in the posterior embryonic end. Among them, Wnt3a has been shown to play relevant roles in the regulation of axial progenitor activity, mesoderm formation and somitogenesis. However, its impact on axial growth remains to be fully understood. Using a transgenic approach in the mouse, we found that the effect of Wnt3a signaling varies depending on the target tissue. High levels of Wnt3a in the epiblast prevented formation of neural tissues, but did not impair axial progenitors from producing different mesodermal lineages...
October 15, 2014: Developmental Biology
Tareck Rharass, Heiko Lemcke, Margareta Lantow, Sergei A Kuznetsov, Dieter G Weiss, Daniela Panáková
Emerging evidence suggests that reactive oxygen species (ROS) can stimulate the Wnt/β-catenin pathway in a number of cellular processes. However, potential sources of endogenous ROS have not been thoroughly explored. Here, we show that growth factor depletion in human neural progenitor cells induces ROS production in mitochondria. Elevated ROS levels augment activation of Wnt/β-catenin signaling that regulates neural differentiation. We find that growth factor depletion stimulates the release of Ca(2+) from the endoplasmic reticulum stores...
October 3, 2014: Journal of Biological Chemistry
Panagiotis Papachristou, Cecilia Dyberg, Maria Lindqvist, Zachi Horn, Thomas Ringstedt
Wnt/beta-catenin signaling plays an important role in neural development, instructing both progenitor cell division and differentiation. During early corticogenesis, Wnt7b is expressed in a restricted expression pattern in the ventricular zone progenitor cells. However, its influence on progenitor cell behavior has not been fully studied. We report that transgenic overexpression of Wnt7b in neural progenitor cells impairs neuronal differentiation and the development of forebrain structures at embryonic day 10...
August 12, 2014: Brain Research
Atsushi Kuwahara, Hiroshi Sakai, Yuanjiang Xu, Yasuhiro Itoh, Yusuke Hirabayashi, Yukiko Gotoh
During mouse neocortical development, the Wnt-β-catenin signaling pathway plays essential roles in various phenomena including neuronal differentiation and proliferation of neural precursor cells (NPCs). Production of the appropriate number of neurons without depletion of the NPC population requires precise regulation of the balance between differentiation and maintenance of NPCs. However, the mechanism that suppresses Wnt signaling to prevent premature neuronal differentiation of NPCs is poorly understood...
2014: PloS One
Carolin Mußmann, Rayk Hübner, Michaela Trilck, Arndt Rolfs, Moritz J Frech
Human neural stem/progenitor cell (hNPC)-derived neuronal progeny has been suggested as a promising cell source in a variety of neurodegenerative diseases. Understanding the underlying mechanisms that regulate neuronal differentiation is essential for efficient cell-based therapies. Wnt and Notch signaling has been shown to be crucial in this process. However, their interactions in the process of neuronal differentiation remain elusive. By using human fetal (ReNcell VM) and iPS-derived hNPCs we demonstrate that Wnt-3a immediately induced a transient HES1 upregulation and a sustained HES5 repression that was accompanied by upregulation of the proneural gene MASH1...
June 15, 2014: Stem Cells and Development
Masanori Yoneyama, Tatsuo Shiba, Shigeru Hasebe, Kasumi Umeda, Taro Yamaguchi, Kiyokazu Ogita
Lithium, a mood stabilizer, is known to ameliorate the stress-induced decrease in hippocampal neurogenesis seen in animal models of stress-related disorders. However, it is unclear whether lithium has beneficial effect on neuronal repair following neuronal damage in neuronal degenerative diseases. Here, we evaluated the effect of in vivo treatment with lithium on the hippocampal neuronal repair in a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampal dentate gyrus (such mice referred to as "impaired animals") [Ogita et al...
2014: PloS One
F Rinaldi, E M Hartfield, L A Crompton, J L Badger, C P Glover, C M Kelly, A E Rosser, J B Uney, M A Caldwell
Connexin43 (Cx43) is the most widely and abundantly expressed gap junction (GJ) protein and it is strongly associated with the regulation of cell cycle progression. Emerging roles for Cx43 in cell adhesion and migration during neural differentiation have also been recently recognized, and this has emphasized the involvement of Cx43 in different physiological process beyond its role as a GJ protein. In this study, we explore the function of Cx43 in the differentiation of human neural progenitor cells (hNPCs) using viral vectors that mediate the overexpression or knockdown of the protein...
2014: Cell Death & Disease
Xijing Zhang, Liangwei Chen, Yazhou Wang, Yinxiu Ding, Zhengwu Peng, Li Duan, Gong Ju, Yi Ren, Xi Wang
Macrophage migration inhibitory factor (MIF) is a highly conserved and evolutionarily ancient mediator with pleiotropic effects. Recent studies demonstrated that the receptors of MIF, including CD44, CXCR2, CXCR4 and CD74, are expressed in the neural stem/progenitor cells (NSPCs). The potential regulatory effect of MIF on NSPCs proliferation and neuronal differentiation, however, is largely unknown. Here, we investigated the effect of MIF on NSPC proliferation and neuronal differentiation, and further examined the signal pathway by which MIF transduced these signal effects in mouse NSPCs in vitro...
2013: International Journal of Biological Sciences
Hideyuki Komori, Qi Xiao, Brooke M McCartney, Cheng-Yu Lee
During asymmetric stem cell division, both the daughter stem cell and the presumptive intermediate progenitor cell inherit cytoplasm from their parental stem cell. Thus, proper specification of intermediate progenitor cell identity requires an efficient mechanism to rapidly extinguish the activity of self-renewal factors, but the mechanisms remain unknown in most stem cell lineages. During asymmetric division of a type II neural stem cell (neuroblast) in the Drosophila larval brain, the Brain tumor (Brat) protein segregates unequally into the immature intermediate neural progenitor (INP), where it specifies INP identity by attenuating the function of the self-renewal factor Klumpfuss (Klu), but the mechanisms are not understood...
January 2014: Development
Jie Chao, Lu Yang, Honghong Yao, Shilpa Buch
Our previous study demonstrated that platelet-derived growth factor-BB (PDGF-BB) increased the cell proliferation of primary rat neuronal progenitor cells (NPCs). However, whether PDGF-BB regulates neurogenesis in HIV-associated neurological disorder (HAND) remains largely unknown. In this study we demonstrated that pre-treatment of NPCs with PDGF-BB restored Tat-mediated impairment of cell proliferation via activation of p38 and JNK MAPK pathways. Moreover, treatment with PDGF-BB induced inactivation of glycogen synthase kinase-3β (GSK-3β), evidenced by its phosphorylation at Ser9, this effect was significantly inhibited by the p38 and JNK inhibitors...
March 2014: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Yuanjie Sun, Nam-Ho Kim, Liting Ji, Seung-Hyuk Kim, Jongho Lee, Hae Jin Rhee
Lysophosphatidic acid (LPA) is a lipid growth factor that regulates diverse cell functions, including cell proliferation, survival and apoptosis. LPA has been demonstrated to be involved in the regulation of cortical neurogenesis by increasing the survival of neural precursors. Previously, we reported that LPA stimulated the inactivation of glycogen synthase kinase 3 (GSK3) via the G protein-coupled LPA1 and LPA2 receptors, by which apoptosis is suppressed in H19-7 cells [an embryonic hippocampal progenitor cell (HPC) line]...
December 2013: Molecular Medicine Reports
George R Flentke, Ana Garic, Marcos Hernandez, Susan M Smith
Prenatal ethanol exposure causes persistent neurodevelopmental deficits by inducing apoptosis within neuronal progenitors including the neural crest. The cellular signaling events underlying this apoptosis are unclear. Using an established chick embryo model, we previously identified ethanol's activation of calmodulin-dependent protein kinase II (CaMKII) as a crucial early step in this pathway. Here, we report that CaMKII is pro-apoptotic because it mediates the loss of transcriptionally active β-catenin, which normally provides trophic support to these cells...
February 2014: Journal of Neurochemistry
Qini Gan, Albert Lee, Ryusuke Suzuki, Takashi Yamagami, Arjun Stokes, Bao Chau Nguyen, David Pleasure, Junjiang Wang, Hong-Wu Chen, Chengji J Zhou
The Wnt/ß-catenin pathway is a critical stem cell regulator and plays important roles in neuroepithelial cells during early gestation. However, the role of Wnt/ß-catenin signaling in radial glia, a major neural stem cell population expanded by midgestation, remains poorly understood. This study shows that genetic ablation of ß-catenin with hGFAP-Cre mice inhibits neocortical formation by disrupting radial glial development. Reduced radial glia and intermediate progenitors are found in the ß-catenin-deficient neocortex during late gestation...
January 2014: Stem Cells
Wei-Qun Fang, Wei-Wei Chen, Amy K Y Fu, Nancy Y Ip
UNLABELLED: The expansion of the mammalian cerebral cortex is safeguarded by a concerted balance between amplification and neuronal differentiation of intermediate progenitors (IPs). Nonetheless, the molecular controls governing these processes remain unclear. We found that the scaffold protein Axin is a critical regulator that determines the IP population size and ultimately the number of neurons during neurogenesis in the developing cerebral cortex. The increase of the IP pool is mediated by the interaction between Axin and GSK-3 in the cytoplasmic compartments of the progenitors...
August 21, 2013: Neuron
Y Zhang, Y Dong, H Zheng, V Shie, H Wang, J J Busscher, Y Yue, Z Xu, Z Xie
Recent population studies suggest that children who receive anesthesia and surgery could be at an increased risk for developing learning disabilities. The underlying reason for this clinical observation is largely unknown. Whether undergoing anesthesia contributes to learning disability development, or if the need for anesthesia and surgery is a marker for other unidentified factors that contribute to the development of learning disabilities, remains to be determined. Neurogenesis, regulated by the Wnt-catenin signaling pathway, has been shown to be involved in learning and memory, and sevoflurane is the most commonly used inhalation anesthetic in children...
November 2013: Current Molecular Medicine
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