Radial Glial Cell

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 3363 Experts worldwide ranked by ideXlab platform

Arnold R Kriegstein - One of the best experts on this subject based on the ideXlab platform.

  • mitotic spindle orientation predicts outer Radial Glial Cell generation in human neocortex
    Nature Communications, 2013
    Co-Authors: Bridget E Lamonica, David V Hansen, Jan H. Lui, Arnold R Kriegstein
    Abstract:

    The human neocortex is increased in size and complexity as compared with most other species. Neocortical expansion has recently been attributed to protracted neurogenesis by outer Radial Glial Cells in the outer subventricular zone, a region present in humans but not in rodents. The mechanisms of human outer Radial Glial Cell generation are unknown, but are proposed to involve division of ventricular Radial Glial Cells; neural stem Cells present in all developing mammals. Here we show that human ventricular Radial Glial Cells produce outer Radial Glial Cells and seed formation of the outer subventricular zone via horizontal divisions, which occur more frequently in humans than in rodents. We further find that outer Radial Glial Cell mitotic behaviour is Cell intrinsic, and that the basal fibre, inherited by outer Radial Glial Cells after ventricular Radial Glial division, determines cleavage angle. Our results suggest that altered regulation of mitotic spindle orientation increased outer Radial Glial Cell number, and ultimately neuronal number, during human brain evolution.

  • mammalian par3 regulates progenitor Cell asymmetric division via notch signaling in the developing neocortex
    Neuron, 2009
    Co-Authors: David R Castanedacastellanos, Ronald S Bultje, Arnold R Kriegstein
    Abstract:

    Summary Asymmetric Cell division of Radial Glial progenitors produces neurons while allowing self-renewal; however, little is known about the mechanism that generates asymmetry in daughter Cell fate specification. Here, we found that mammalian partition defective protein 3 (mPar3), a key Cell polarity determinant, exhibits dynamic distribution in Radial Glial progenitors. While it is enriched at the lateral membrane domain in the ventricular endfeet during interphase, mPar3 becomes dispersed and shows asymmetric localization as Cell cycle progresses. Either removal or ectopic expression of mPar3 prevents Radial Glial progenitors from dividing asymmetrically yet generates different outcomes in daughter Cell fate specification. Furthermore, the expression level of mPar3 affects Notch signaling, and manipulations of Notch signaling or Numb expression suppress mPar3 regulation of Radial Glial Cell division and daughter Cell fate specification. These results reveal a critical molecular pathway underlying asymmetric Cell division of Radial Glial progenitors in the mammalian neocortex.

  • calcium waves propagate through Radial Glial Cells and modulate proliferation in the developing neocortex
    Neuron, 2004
    Co-Authors: Tamily A Weissman, Patricio A Riquelme, Lidija Ivic, Alexander C Flint, Arnold R Kriegstein
    Abstract:

    Abstract The majority of neurons in the adult neocortex are produced embryonically during a brief but intense period of neuronal proliferation. The Radial Glial Cell, a transient embryonic Cell type known for its crucial role in neuronal migration, has recently been shown to function as a neuronal progenitor Cell and appears to produce most cortical pyramidal neurons. Radial Glial Cell modulation could thus affect neuron production, neuronal migration, and overall cortical architecture; however, signaling mechanisms among Radial glia have not been studied directly. We demonstrate here that calcium waves propagate through Radial Glial Cells in the proliferative cortical ventricular zone (VZ). Radial Glial calcium waves occur spontaneously and require connexin hemichannels, P2Y 1 ATP receptors, and intraCellular IP 3 -mediated calcium release. Furthermore, we show that wave disruption decreases VZ proliferation during the peak of embryonic neurogenesis. Taken together, these results demonstrate a Radial Glial signaling mechanism that may regulate cortical neuronal production.

E S Anton - One of the best experts on this subject based on the ideXlab platform.

  • marcks modulates Radial progenitor placement proliferation and organization in the developing cerebral cortex
    Development, 2009
    Co-Authors: Jill M Weimer, Yukako Yokota, Amelia Stanco, Deborah J Stumpo, Perry J Blackshear, E S Anton
    Abstract:

    The Radial Glial Cells serve as neural progenitors and as a migratory guide for newborn neurons in the developing cerebral cortex. These functions require appropriate organization and proliferation of the polarized Radial Glial scaffold. Here, we demonstrate in mice that the myristoylated alanine-rich C-kinase substrate protein (MARCKS), a prominent Cellular substrate for PKC, modulates Radial Glial placement and expansion. Loss of MARCKS results in ectopic collection of mitotically active Radial progenitors away from the ventricular zone (VZ) in the upper cerebral wall. Apical restriction of key polarity complexes [CDC42, beta-catenin (CTNNB1), N-cadherin (CDH2), myosin IIB (MYOIIB), aPKCzeta, LGL, PAR3, pericentrin, PROM1] is lost. Furthermore, the Radial Glial scaffold in Marcks null cortex is compromised, with discontinuous, non-Radial processes apparent throughout the cerebral wall and deformed, bulbous, unbranched end-feet at the basal ends. Further, the density of Radial processes within the cerebral cortex is reduced. These deficits in Radial Glial development culminate in aberrant positioning of neurons and disrupted cortical lamination. Genetic rescue experiments demonstrate, surprisingly, that phosphorylation of MARCKS by PKC is not essential for the role of MARCKS in Radial Glial Cell development. By contrast, the myristoylation domain of MARCKS needed for membrane association is essential for MARCKS function in Radial glia. The membrane-associated targeting of MARCKS and the resultant polarized distribution of signaling complexes essential for apicobasal polarity may constitute a critical event in the appropriate placement, proliferation and organization of polarized Radial Glial scaffold in the developing cerebral cortex.

  • neuregulin 1 erbb2 signaling is required for the establishment of Radial glia and their transformation into astrocytes in cerebral cortex
    Proceedings of the National Academy of Sciences of the United States of America, 2003
    Co-Authors: Ralf S Schmid, M A Marchionni, Barbara Mcgrath, Bridget E Berechid, Becky Boyles, Nenad Sestan, E S Anton
    Abstract:

    Radial Glial Cells and astrocytes function to support the construction and maintenance, respectively, of the cerebral cortex. However, the mechanisms that determine how Radial Glial Cells are established, maintained, and transformed into astrocytes in the cerebral cortex are not well understood. Here, we show that neuregulin-1 (NRG-1) exerts a critical role in the establishment of Radial Glial Cells. Radial Glial Cell generation is significantly impaired in NRG mutants, and this defect can be rescued by exogenous NRG-1. Down-regulation of expression and activity of erbB2, a member of the NRG-1 receptor complex, leads to the transformation of Radial Glial Cells into astrocytes. Reintroduction of erbB2 transforms astrocytes into Radial glia. The activated form of the Notch1 receptor, which promotes the Radial Glial phenotype, activates the erbB2 promoter in Radial Glial Cells. These results suggest that developmental changes in NRG-1–erbB2 interactions modulate the establishment of Radial glia and contribute to their appropriate transformation into astrocytes.

  • role of ggf neuregulin signaling in interactions between migrating neurons and Radial glia in the developing cerebral cortex
    Development, 1997
    Co-Authors: E S Anton, M A Marchionni, Kuofen Lee, Pasko Rakic
    Abstract:

    During neuronal migration to the developing cerebral cortex, neurons regulate Radial Glial Cell function and Radial Glial Cells, in turn, support neuronal Cell migration and differentiation. To study how migrating neurons and Radial Glial Cells influence each others' function in the developing cerebral cortex, we examined the role of Glial growth factor (a soluble form of neuregulin), in neuron-Radial Glial interactions. Here, we show that GGF is expressed by migrating cortical neurons and promotes their migration along Radial Glial fibers. Concurrently, GGF also promotes the maintenance and elongation of Radial Glial Cells, which are essential for guiding neuronal migration to the cortex. In the absence of GGF signaling via erbB2 receptors, Radial Glial development is abnormal. Furthermore, GGF's regulation of Radial Glial development is mediated in part by brain lipid-binding protein (BLBP), a neuronally induced, Radial Glial molecule, previously shown to be essential for the establishment and maintenance of Radial Glial fiber system. The ability of GGF to influence both neuronal migration and Radial Glial development in a mutually dependent manner suggests that it functions as a mediator of interactions between migrating neurons and Radial Glial Cells in the developing cerebral cortex.

Francois Brion - One of the best experts on this subject based on the ideXlab platform.

  • several synthetic progestins disrupt the Glial Cell specific brain aromatase expression in developing zebra fish
    Toxicology and Applied Pharmacology, 2016
    Co-Authors: Joel Canonicolau, Clementine Garoche, Nathalie Hinfray, Elisabeth Pellegrini, Noureddine Boujrad, Farzad Pakdel, Olivier Kah, Francois Brion
    Abstract:

    The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the Glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC50 ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a Radial Glial Cell context using U251-MG Cells co-transfected with zebrafish ER subtypes (zfERα, zfERβ1 or zfERβ2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in Radial Glial Cells. Given the crucial role of Radial Glial Cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation.

Michael Piper - One of the best experts on this subject based on the ideXlab platform.

  • the association of microcephaly protein wdr62 with cpap ift88 is required for cilia formation and neocortical development
    Human Molecular Genetics, 2020
    Co-Authors: Belal Shohayeb, Yvonne Y C Yeap, S. Sean Millard, Robert G. Parton, Michael Piper
    Abstract:

    WDR62 mutations that result in protein loss, truncation or single amino-acid substitutions are causative for human microcephaly, indicating critical roles in Cell expansion required for brain development. WDR62 missense mutations that retain protein expression represent partial loss-of-function mutants that may therefore provide specific insights into Radial Glial Cell processes critical for brain growth. Here we utilized CRISPR/Cas9 approaches to generate three strains of WDR62 mutant mice; WDR62V66M/V66M and WDR62R439H/R439H mice recapitulate conserved missense mutations found in humans with microcephaly, with the third strain being a null allele (WDR62stop/stop). Each of these mutations resulted in embryonic lethality to varying degrees and gross morphological defects consistent with ciliopathies (dwarfism, anopthalamia and microcephaly). We find that WDR62 mutant proteins (V66M and R439H) localize to the basal body but fail to recruit CPAP. As a consequence, we observe deficient recruitment of IFT88, a protein that is required for cilia formation. This underpins the maintenance of Radial glia as WDR62 mutations caused premature differentiation of Radial glia resulting in reduced generation of neurons and cortical thinning. These findings highlight the important role of the primary cilium in neocortical expansion and implicates ciliary dysfunction as underlying the pathology of MCPH2 patients.

  • The association of microcephaly protein WDR62 with CPAP/IFT88 is required for cilia formation and neocortical development
    Human molecular genetics, 2019
    Co-Authors: Belal Shohayeb, Yvonne Y C Yeap, S. Sean Millard, Robert G. Parton, Michael Piper
    Abstract:

    WDR62 mutations that result in protein loss, truncation or single amino-acid substitutions are causative for human microcephaly, indicating critical roles in Cell expansion required for brain development. WDR62 missense mutations that retain protein expression represent partial loss-of-function mutants that may therefore provide specific insights into Radial Glial Cell processes critical for brain growth. Here we utilized CRISPR/Cas9 approaches to generate three strains of WDR62 mutant mice; WDR62V66M/V66M and WDR62R439H/R439H mice recapitulate conserved missense mutations found in humans with microcephaly, with the third strain being a null allele (WDR62stop/stop). Each of these mutations resulted in embryonic lethality to varying degrees and gross morphological defects consistent with ciliopathies (dwarfism, anopthalamia and microcephaly). We find that WDR62 mutant proteins (V66M and R439H) localize to the basal body but fail to recruit CPAP. As a consequence, we observe deficient recruitment of IFT88, a protein that is required for cilia formation. This underpins the maintenance of Radial glia as WDR62 mutations caused premature differentiation of Radial glia resulting in reduced generation of neurons and cortical thinning. These findings highlight the important role of the primary cilium in neocortical expansion and implicates ciliary dysfunction as underlying the pathology of MCPH2 patients.

Joel Canonicolau - One of the best experts on this subject based on the ideXlab platform.

  • several synthetic progestins disrupt the Glial Cell specific brain aromatase expression in developing zebra fish
    Toxicology and Applied Pharmacology, 2016
    Co-Authors: Joel Canonicolau, Clementine Garoche, Nathalie Hinfray, Elisabeth Pellegrini, Noureddine Boujrad, Farzad Pakdel, Olivier Kah, Francois Brion
    Abstract:

    The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the Glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC50 ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a Radial Glial Cell context using U251-MG Cells co-transfected with zebrafish ER subtypes (zfERα, zfERβ1 or zfERβ2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in Radial Glial Cells. Given the crucial role of Radial Glial Cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation.