Radial Glial Identity Is Promoted by Notch1 Signaling in the Murine Forebrain

In vertebrates, Notch signaling is generally thought to inhibit neural differentiation. However, whether Notch can also promote specific early cell fates in this context is unknown. We introduced activated Notch1 (NIC) into the mouse forebrain, before the onset of neurogenesis, using a retroviral vector and ultrasound imaging. During embryogenesis, NIC-infected cells became radial glia, the first specialized cell type evident in the forebrain. Thus, rather than simply inhibiting differentiation, Notch1 signaling promoted the acquisition of an early cellular phenotype. Postnatally, many NIC-infected cells became periventricular astrocytes, cells previously shown to be neural stem cells in the adult. These results suggest that Notch1 promotes radial glial identity during embryogenesis, and that radial glia may be lineally related to stem cells in the adult nervous system.

[1]  P. Rakic,et al.  Arrested proliferation of radial glial cells during midgestation in rhesus monkey , 1979, Nature.

[2]  Daniel A. Lim,et al.  Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain , 1999, Cell.

[3]  S. Artavanis-Tsakonas,et al.  Specific truncations of Drosophila Notch define dominant activated and dominant negative forms of the receptor , 1993, Cell.

[4]  M. Götz,et al.  Pax6 Controls Radial Glia Differentiation in the Cerebral Cortex , 1998, Neuron.

[5]  Raphael Kopan,et al.  Developmental Signalling: Vertebrate ligands for Notch , 1995, Current Biology.

[6]  V S Caviness,et al.  Identification of radial glial cells within the developing murine central nervous system: studies based upon a new immunohistochemical marker. , 1988, Brain research. Developmental brain research.

[7]  J. Rossant,et al.  Conservation of the Notch signalling pathway in mammalian neurogenesis. , 1997, Development.

[8]  R. McKay,et al.  CNS stem cells express a new class of intermediate filament protein , 1990, Cell.

[9]  S. Artavanis-Tsakonas,et al.  Notch Signaling : Cell Fate Control and Signal Integration in Development , 1999 .

[10]  U. Lendahl,et al.  Expression of the Notch 3 intracellular domain in mouse central nervous system progenitor cells is lethal and leads to disturbed neural tube development , 1996, Mechanisms of Development.

[11]  Jonas Frisén,et al.  Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System , 1999, Cell.

[12]  Brent A. Reynolds,et al.  Neural stem cells in the adult mammalian forebrain: A relatively quiescent subpopulation of subependymal cells , 1994, Neuron.

[13]  J. Boulter,et al.  Expression Patterns ofJagged, Delta1, Notch1, Notch2,andNotch3Genes Identify Ligand–Receptor Pairs That May Function in Neural Development , 1996, Molecular and Cellular Neuroscience.

[14]  S. Cajal,et al.  Histology of the Nervous System , 1911 .

[15]  J. Sanes,et al.  Lineage of radial glia in the chicken optic tectum. , 1992, Development.

[16]  Daniel H. Turnbull,et al.  A method for rapid gain-of-function studies in the mouse embryonic nervoussystem , 1999, Nature Neuroscience.

[17]  P. Rakic.  Radial versus tangential migration of neuronal clones in the developing cerebral cortex. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. H. Angelis,et al.  Maintenance of somite borders in mice requires the Delta homologue Dll1 , 1997, Nature.

[19]  N. Heintz,et al.  Differentiating neurons activate transcription of the brain lipid-binding protein gene in radial glia through a novel regulatory element. , 1995, Development.

[20]  P. Rakić.  Guidance of neurons migrating to the fetal monkey neocortex. , 1971, Brain research.

[21]  R. Kageyama,et al.  Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects. , 1995, Genes & development.

[22]  H. Roehl,et al.  Control of cell fate in C. elegans by a GLP-1 peptide consisting primarily of ankyrin repeats , 1993, Nature.

[23]  M. Hatten,et al.  Riding the glial monorail: A common mechanism for glialguided neuronal migration in different regions of the developing mammalian brain , 1990, Trends in Neurosciences.

[24]  B. Barres,et al.  Notch Receptor Activation Inhibits Oligodendrocyte Differentiation , 1998, Neuron.

[25]  L. Lapham,et al.  Radial glia in the human fetal cerebrum: A combined golgi, immunofluorescent and electron microscopic study , 1978, Brain Research.

[26]  Fernando Nottebohm,et al.  Proliferation “hot spots” in adult avian ventricular zone reveal radial cell division , 1990, Neuron.

[27]  P. Rakic,et al.  Role of GGF/neuregulin signaling in interactions between migrating neurons and radial glia in the developing cerebral cortex. , 1997, Development.

[28]  Raphael Kopan,et al.  An activated Notch suppresses neurogenesis and myogenesis but not gliogenesis in mammalian cells. , 1994, Development.

[29]  P. Rakić.  Mode of cell migration to the superficial layers of fetal monkey neocortex , 1972, The Journal of comparative neurology.

[30]  C. Cepko,et al.  The Expression and Function of Notch Pathway Genes in the Developing Rat Eye , 1997, The Journal of Neuroscience.

[31]  T Takahashi,et al.  The Leaving or Q Fraction of the Murine Cerebral Proliferative Epithelium: A General Model of Neocortical Neuronogenesis , 1996, The Journal of Neuroscience.

[32]  J. Nye.  The Notch proteins , 1999, Current Biology.

[33]  V. Caviness,et al.  The alignment of migrating neural cells in relation to the murine neopallial radial glial fiber system. , 1991, Cerebral cortex.

[34]  P. Rakić,et al.  Early divergence and changing proportions of neuronal and glial precursor cells in the primate cerebral ventricular zone. , 1983, Developmental biology.

[35]  G. Weinmaster,et al.  The Ins and Outs of Notch Signaling , 1997, Molecular and Cellular Neuroscience.

[36]  Anirvan Ghosh,et al.  Nuclear Notch1 signaling and the regulation of dendritic development , 2000, Nature Neuroscience.

[37]  H. Toresson,et al.  Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation. , 1999, Development.

[38]  M. Hatten,et al.  Brain lipid-binding protein (BLBP): A novel signaling system in the developing mammalian CNS , 1994, Neuron.

[39]  T. Voigt.  Development of glial cells in the cerebral wall of ferrets: Direct tracing of their transformation from radial glia into astrocytes , 1989, The Journal of comparative neurology.

[40]  G. Weinmaster,et al.  Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice. , 1998, Genes & development.

[41]  R. McKay,et al.  Immortalization of precursor cells from the mammalian CNS , 1988, Neuron.

[42]  J. Lewis,et al.  Notch signalling and the control of cell fate choices in vertebrates. , 1998, Seminars in cell & developmental biology.

[43]  J. Franklin,et al.  Autonomous and non-autonomous regulation of mammalian neurite development by Notch1 and Delta1 , 1999, Current Biology.

[44]  G. Struhl,et al.  Intrinsic activity of the lin-12 and Notch intracellular domains in vivo , 1993, Cell.

[45]  Daniel H Turnbull,et al.  Alteration of limb and brain patterning in early mouse embryos by ultrasound-guided injection of Shh-expressing cells , 1998, Mechanisms of Development.

[46]  M. Jacobson,et al.  Embryonic vertebrate central nervous system: Revised terminology , 1970 .

[47]  W. Harris,et al.  Xotch inhibits cell differentiation in the xenopus retina , 1995, Neuron.

[48]  D. van der Kooy,et al.  Adult Mammalian Forebrain Ependymal and Subependymal Cells Demonstrate Proliferative Potential, but only Subependymal Cells Have Neural Stem Cell Characteristics , 1999, The Journal of Neuroscience.

[49]  P. Rakic,et al.  Contact-dependent inhibition of cortical neurite growth mediated by notch signaling. , 1999, Science.

[50]  K. Moriyoshi,et al.  Persistent expression of helix‐loop‐helix factor HES‐1 prevents mammalian neural differentiation in the central nervous system. , 1994, The EMBO journal.

[51]  T. Mak,et al.  Disruption of the mouse RBP-J kappa gene results in early embryonic death. , 1995, Development.

[52]  Daniel H Turnbull,et al.  Specification of Mouse Telencephalic and Mid-Hindbrain Progenitors Following Heterotopic Ultrasound-Guided Embryonic Transplantation , 1997, Neuron.

[53]  P. Rakic.  Specification of cerebral cortical areas. , 1988, Science.