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External granule layer EGL

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https://www.readbyqxmd.com/read/29030097/transient-vimentin-expression-during-the-embryonic-development-of-the-chicken-cerebellum
#1
Vasiliki Kommata, Catherine R Dermon
Complex morphogenetic events, critical for the development of normal cerebellum foliation and layering, are known to involve type III intermediate filament protein such as vimentin expressed by Bergmann glia. The present study aimed to determine aspects of intermediate and late embryonic pattern of vimentin expression during the corticogenesis of chicken cerebellum at embryonic days 10-19 (E10-E19), using single and double immunohistochemistry/immunofluorescence. Vimentin expression showed partial co-localization with the glial markers GFAP and BLBP...
October 13, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28974424/lkb1-regulates-granule-cell-migration-and-cortical-folding-of-the-cerebellar-cortex
#2
Kaitlyn E Ryan, Patrick S Kim, Jonathan T Fleming, Emily Brignola, Frances Y Cheng, Ying Litingtung, Chin Chiang
Cerebellar growth and foliation require the Hedgehog-driven proliferation of granule cell precursors (GCPs) in the external granule layer (EGL). However, that increased or extended GCP proliferation generally does not elicit ectopic folds suggests that additional determinants control cortical expansion and foliation during cerebellar development. Here, we find that genetic loss of the serine-threonine kinase Liver Kinase B1 (Lkb1) in GCPs increased cerebellar cortical size and foliation independent of changes in proliferation or Hedgehog signaling...
December 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28939329/potential-deficit-from-decreased-cerebellar-granule-cell-migration-in-serine-racemase-deficient-mice-is-reversed-by-increased-expression-of-glun2b-and-elevated-levels-of-nmdar-agonists
#3
He Zhang, Liping Song, Yuhua Chang, Mengjuan Wu, Xiuli Kuang, Haiyan Jiang, Shengzhou Wu
Inward migration of cerebellar granule cells (CGCs) after birth is critical for lamination in the cerebellar cortex. N-methyl-d-aspartate (NMDA) subtype of glutamate receptor (NMDAR) tethering CGCs into Bergmann glial fibers mediates the inward movement during the glial-dependent migratory phase. Activation of NMDAR depends on simultaneous binding of the GluN2 subunit by glutamate, and of the GluN1 subunit by d-serine or glycine; d-serine is believed to be an endogenous ligand of NMDAR. We hypothesized that lamination of the cerebellar cortex may be compromised in Srr (the gene for serine racemase (SR)) mutated mice (Srrnull) because of significantly low levels of d-serine per se...
September 20, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28633908/dynamics-of-the-cell-division-orientation-of-granule-cell-precursors-during-cerebellar-development
#4
Satoshi Miyashita, Toma Adachi, Mariko Yamashita, Takayuki Sota, Mikio Hoshino
The cerebellar granule cell (GC) system provides a good model for studying neuronal development. In the external granule layer (EGL), granule cell precursors (GCPs) rapidly and continuously divide to produce numerous GCs as well as GCPs. In some brain regions, the orientation of cell division affects daughter cell fate, thus the direction of GCP division is related to whether it produces a GCP or a GC. Therefore, we tried to characterize the orientation of GCP division from embryonic to postnatal stages and to identify an environmental cue that regulates the orientation...
October 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28512198/novel-role-of-rac-mid1-signaling-in-medial-cerebellar-development
#5
Takashi Nakamura, Takehiko Ueyama, Yuzuru Ninoyu, Hirofumi Sakaguchi, Narantsog Choijookhuu, Yoshitaka Hishikawa, Hiroshi Kiyonari, Masaaki Kohta, Mizuho Sakahara, Ivan de Curtis, Eiji Kohmura, Yasuo Hisa, Atsu Aiba, Naoaki Saito
Rac signaling impacts a relatively large number of downstream targets; however, few studies have established an association between Rac pathways and pathological conditions. In the present study, we generated mice with double knockout of Rac1 and Rac3 (Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) ) in cerebellar granule neurons (CGNs). We observed impaired tangential migration at E16.5, as well as numerous apoptotic CGNs at the deepest layer of the external granule layer (EGL) in the medial cerebellum of Atoh1-Cre;Rac1(flox/flox);Rac3(-/-) mice at P8...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28483977/uncoupling-of-unc5c-with-polymerized-tubb3-in-microtubules-mediates-netrin-1-repulsion
#6
Qiangqiang Shao, Tao Yang, Huai Huang, Farrah Alarmanazi, Guofa Liu
Modulation of microtubule (MT) dynamics is a key event of cytoskeleton remodeling in the growth cone (GC) during axon outgrowth and pathfinding. Our previous studies have shown that the direct interaction of netrin receptor DCC and DSCAM with polymerized TUBB3, a neuron-specific MT subunit in the brain, is required for netrin-1-mediated axon outgrowth, branching, and attraction. Here, we show that uncoupling of polymerized TUBB3 with netrin-1-repulsive receptor UNC5C is involved in netrin-1-mediated axonal repulsion...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28450263/wls-expression-in-the-rhombic-lip-orchestrates-the-embryonic-development-of-the-mouse-cerebellum
#7
Joanna Yeung, Daniel Goldowitz
Wntless (Wls) is implicated in the Wnt signaling pathway by regulating the secretion of Wnt molecules. During brain development, Wls is expressed in the isthmic organizer (ISO) and rhombic lip (RL). Wls regulates Wnt1 secretion at the ISO which is required to induce midbrain-hindbrain structures. However, Wls function in the RL is not known. Here, we employed Nestin-cre to delete Wls specifically in the RL during mid-gestation. The loss-of-Wls leads to an abnormal RL during development and cerebellar vermis hypoplasia at birth...
April 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28448983/intrauterine-growth-restriction-alters-the-postnatal-development-of-the-rat-cerebellum
#8
Annie R A McDougall, Vanny Wiradjaja, Aminath Azhan, Anqi Li, Nadia Hale, Mary E Wlodek, Stuart B Hooper, Megan J Wallace, Mary Tolcos
Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0...
2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28382975/radiation-induces-progenitor-cell-death-microglia-activation-and-blood-brain-barrier-damage-in-the-juvenile-rat-cerebellum
#9
Kai Zhou, Martina Boström, C Joakim Ek, Tao Li, Cuicui Xie, Yiran Xu, Yanyan Sun, Klas Blomgren, Changlian Zhu
Posterior fossa tumors are the most common childhood intracranial tumors, and radiotherapy is one of the most effective treatments. However, irradiation induces long-term adverse effects that can have significant negative impacts on the patient's quality of life. The purpose of this study was to characterize irradiation-induced cellular and molecular changes in the cerebellum. We found that irradiation-induced cell death occurred mainly in the external germinal layer (EGL) of the juvenile rat cerebellum. The number of proliferating cells in the EGL decreased, and 82...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27734996/stem-progenitor-cells-in-the-developing-human-cerebellum-an-immunohistochemical-study
#10
V Pibiri, A Ravarino, C Gerosa, M C Pintus, V Fanos, G Faa
The aim of this study was to analyze, by immunohistochemistry, the occurrence of stem/progenitor cells localized in the different niches of the developing human cerebellum. To this end, cerebellar samples were obtained from 3 fetuses and 3 newborns ranging, respectively, from 11 to 24 and from 30 to 38 weeks of gestation. Specimens were 10% formalin-fixed, routinely processed and paraffin-embedded; 3 μm-tick sections were immunostained with anti-SOX2 and PAX6 antibodies. Our study evidenced SOX2 and PAX6 immunoreactivity in precursors cells in all six developing human cerebella...
September 19, 2016: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/27601242/developmental-injury-to-the-cerebellar-cortex-following-hydroxyurea-treatment-in-early-postnatal-life-an-immunohistochemical-and-electron-microscopic-study
#11
Joaquín Martí, Vanesa Molina, M C Santa-Cruz, José P Hervás
Postnatal development of the cerebellar cortex was studied in rats administered with a single dose (2 mg/g) of the cytotoxic agent hydroxyurea (HU) on postnatal day (P) 9 and collected at appropriate times ranging from 6 h to 45 days. Quantification of several parameters such as the density of pyknotic, mitotic, BrdU-positive, and vimentin-stained cells revealed that HU compromises the survival of the external granular layer (EGL) cells. Moreover, vimentin immunocytochemistry revealed overexpression and thicker immunoreactive glial processes in HU-treated rats...
February 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/27444290/shh-desmoplastic-nodular-medulloblastoma-and-gorlin-syndrome-in-the-setting-of-down-syndrome-case-report-molecular-profiling-and-review-of-the-literature
#12
REVIEW
Ross Mangum, Elizabeth Varga, Daniel R Boué, David Capper, Martin Benesch, Jeffrey Leonard, Diana S Osorio, Christopher R Pierson, Nicholas Zumberge, Felix Sahm, Daniel Schrimpf, Stefan M Pfister, Jonathan L Finlay
INTRODUCTION: Individuals with Down syndrome (DS) have an increased risk of acute leukemia compared to a markedly decreased incidence of solid tumors. Medulloblastoma, the most common malignant brain tumor of childhood, is particularly rare in the DS population, with only one published case. As demonstrated in a mouse model, DS is associated with cerebellar hypoplasia and a decreased number of cerebellar granule neuron progenitor cells (CGNPs) in the external granule cell layer (EGL)...
December 2016: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/27434667/proneurotrophin-3-promotes-cell-cycle-withdrawal-of-developing-cerebellar-granule-cell-progenitors-via-the-p75-neurotrophin-receptor
#13
Juan Pablo Zanin, Elizabeth Abercrombie, Wilma J Friedman
Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury...
2016: ELife
https://www.readbyqxmd.com/read/27125657/a-mathematical-model-of-granule-cell-generation-during-mouse-cerebellum-development
#14
Shoshana R Leffler, Emilie Legué, Orlando Aristizábal, Alexandra L Joyner, Charles S Peskin, Daniel H Turnbull
Determining the cellular basis of brain growth is an important problem in developmental neurobiology. In the mammalian brain, the cerebellum is particularly amenable to studies of growth because it contains only a few cell types, including the granule cells, which are the most numerous neuronal subtype. Furthermore, in the mouse cerebellum granule cells are generated from granule cell precursors (gcps) in the external granule layer (EGL), from 1 day before birth until about 2 weeks of age. The complexity of the underlying cellular processes (multiple cell behaviors, three spatial dimensions, time-dependent changes) requires a quantitative framework to be fully understood...
May 2016: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/27086929/wip1-modulates-responsiveness-to-sonic-hedgehog-signaling-in-neuronal-precursor-cells-and-medulloblastoma
#15
J Wen, J Lee, A Malhotra, R Nahta, A R Arnold, M C Buss, B D Brown, C Maier, A M Kenney, M Remke, V Ramaswamy, M D Taylor, R C Castellino
High-level amplification of the protein phosphatase PPM1D (WIP1) is present in a subset of medulloblastomas (MBs) that have an expression profile consistent with active Sonic Hedgehog (SHH) signaling. We found that WIP1 overexpression increased expression of Shh target genes and cell proliferation in response to Shh stimulation in NIH3T3 and cerebellar granule neuron precursor cells in a p53-independent manner. Thus, we developed a mouse in which WIP1 is expressed in the developing brain under control of the Neurod2 promoter (ND2:WIP1)...
October 20, 2016: Oncogene
https://www.readbyqxmd.com/read/27039094/overexpression-of-lin28b-in-neural-stem-cells-is-insufficient-for-brain-tumor-formation-but-induces-pathological-lobulation-of-the-developing-cerebellum
#16
Annika K Wefers, Sven Lindner, Johannes H Schulte, Ulrich Schüller
LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene expression during development and carcinogenesis. It is strongly upregulated in a variety of brain tumors, such as medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or glioblastoma, but the effect of an in vivo overexpression of LIN28B on the developing central nervous system is unknown. We generated transgenic mice that either overexpressed Lin28b in Math1-positive cerebellar granule neuron precursors or in a broad range of Nestin-positive neural precursors...
February 2017: Cerebellum
https://www.readbyqxmd.com/read/26709704/ex-vivo-culture-of-chick-cerebellar-slices-and-spatially-targeted-electroporation-of-granule-cell-precursors
#17
Michalina Hanzel, Richard J T Wingate, Thomas Butts
The cerebellar external granule layer (EGL) is the site of the largest transit amplification in the developing brain, and an excellent model for studying neuronal proliferation and differentiation. In addition, evolutionary modifications of its proliferative capability have been responsible for the dramatic expansion of cerebellar size in the amniotes, making the cerebellum an excellent model for evo-devo studies of the vertebrate brain. The constituent cells of the EGL, cerebellar granule progenitors, also represent a significant cell of origin for medulloblastoma, the most prevalent paediatric neuronal tumour...
December 14, 2015: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/26657772/the-apical-complex-protein-pals1-is-required-to-maintain-cerebellar-progenitor-cells-in-a-proliferative-state
#18
Jun Young Park, Lucinda J Hughes, Uk Yeol Moon, Raehee Park, Sang-Bae Kim, Khoi Tran, Ju-Seog Lee, Seo-Hee Cho, Seonhee Kim
Through their biased localization and function within the cell, polarity complex proteins are necessary to establish the cellular asymmetry required for tissue organization. Well-characterized germinal zones, mitogenic signals and cell types make the cerebellum an excellent model for addressing the crucial function of polarity complex proteins in the generation and organization of neural tissues. Deletion of the apical polarity complex protein Pals1 in the developing cerebellum results in a remarkably undersized cerebellum with disrupted layers in poorly formed folia and strikingly reduced granule cell production...
January 1, 2016: Development
https://www.readbyqxmd.com/read/26640242/vitronectin-promotes-the-progress-of-the-initial-differentiation-stage-in-cerebellar-granule-cells
#19
Kei Hashimoto, Fumi Sakane, Natsumi Ikeda, Ayumi Akiyama, Miyaka Sugahara, Yasunori Miyamoto
Vitronectin (VN), which is an extracellular matrix protein, is known to be involved in the proliferation and differentiation of primary cultured cerebellar granule cell precursors (CGCPs); however, the effect of VN is not fully understood. In this study, we analyzed the effects of VN loss on the proliferation and differentiation of CGCPs in VN knockout (VNKO) mice in vivo. First, immunohistochemistry showed that VN was distributed in the region from the inner external granule layer (iEGL) through the internal granule layer (IGL) in wild-type (WT) mice...
January 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/26524254/altered-cerebellum-development-and-impaired-motor-coordination-in-mice-lacking-the-btg1-gene-involvement-of-cyclin-d1
#20
Manuela Ceccarelli, Laura Micheli, Giorgio D'Andrea, Marco De Bardi, Blanca Scheijen, MariaTeresa Ciotti, Luca Leonardi, Siro Luvisetto, Felice Tirone
Cerebellar granule neurons develop postnatally from cerebellar granule precursors (GCPs), which are located in the external granule layer (EGL) where they massively proliferate. Thereafter, GCPs become postmitotic, migrate inward to form the internal granule layer (IGL), further differentiate and form synapses with Purkinje cell dendrites. We previously showed that the Btg family gene, Tis21/Btg2, is required for normal GCP migration. Here we investigated the role in cerebellar development of the related gene, Btg1, which regulates stem cell quiescence in adult neurogenic niches, and is expressed in the cerebellum...
December 1, 2015: Developmental Biology
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