Radial glial identity is promoted by Notch1 signaling in the murine forebrain.

By N. Gaiano, J. Nye, G. Fishell. Neuron, 2000

783 citations recorded by the source corpus.

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.

Subfields: Cancer Research, Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/beaee17cb8a29f5efebeaa54e4b50ca78ae1da95

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Citations in the corpus

Human ES cell-derived neural rosettes reveal a functionally distinct early neural stem cell stage. (2008, background): “Genetic evidence in mouse development suggests that Notch1 signaling promotes radial glia identity (Gaiano et al. 2000).”
Tumorigenesis in the brain: location, location, location. (2007, background): “The CSC hypothesis is predicated on the idea that not all cancer cells have equal proliferative potential, and that cells with the greatest ability to proliferate and form new tumors have phenotypic and functional properties similar to NSCs.”
Brain micro-ecologies: neural stem cell niches in the adult mammalian brain (2008, background): “Over-expression of activated Notch1 in the embryonic brain or of activated Notch1 or 3 in adult cultured hippocampal progenitors leads to the generation of astrocytes (Gaiano et al. 2000; Chambers et al. 2001; Tanigaki et al. 2001).”
For the long run: maintaining germinal niches in the adult brain. (2004, neutral): “5 is primarily important forpostnatally (Gaiano et al., 2000).”
The role of notch in promoting glial and neural stem cell fates. (2002, background): “…have suggested that rather than simply inhibiting neuronal differentiation and maintaining a neural progenitor state, Notch may, in some contexts, promote the acquisition of glial identity (Furukawa et al. 2000, Gaiano et al. 2000, Hojo et al. 2000, Morrison et al. 2000, Scheer et al. 2001).”
The Hes gene family: repressors and oscillators that orchestrate embryogenesis (2007, background): “The intracellular domain of Notch (NICD), which is constitutively active, also promotes the maintenance of radial glial cells by inhibiting neurogenesis (Gaiano et al., 2000).”
Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. (2000, positive): “…were isolated by their green fluorescence from E14 cortex and analyzed directly after the sort, we detected 80% precursor cells as marked by Ki67 (Gerdes et al., 1997) and nestin (Frederiksen and McKay, 1988) immunoreactivity, and the absence of staining with β-tubulin-III-antiserum (Lee et al.,…”
Development and Evolution of the Human Neocortex (2011, positive): “Overexpression of the activated Notch intracellular domain (NICD) results in increased numbers of cells expressing RG markers, showing functionally that Notch activation is associated with the RG state (Gaiano et al., 2000).”
Astrocytes Give Rise to New Neurons in the Adult Mammalian Hippocampus (2001, background): “In mammals, they have been generally considered committed progenitors of astrocytes (Schmechel and Rakic, 1979), but recent evidence in the developing mammalian brain indicates that radial glia can give rise to new neurons and may correspond to neural stem cells ( Gaiano et al., 2000; Malatesta et ”
Notch signaling: from the outside in. (2000, background): “…been suggested that Notch can directly specify glial cell fates rather than simply inhibit neuronal differentiation (Furukawa et al., 2000; Gaiano et al., 2000; Morrison et al., 2000); however, direct proof of this proposal awaits identification of Notch-regulated factors required for…”
HES and HERP families: Multiple effectors of the notch signaling pathway (2003, background): “Several groups have reported that Notch1 and its effectors, HES1 and HES5, may play an instructive role in actively promoting gliogenesis rather than simply inhibiting neuronal differentiation (Furukawa et al., 2000; Gaiano et al., 2000; Hojo et al., 2000; Morrison et al., 2000).”
Cell migration in the forebrain. (2003, background): “After neuronal production ceases, radial glial cells retract their ventricular and pial attachments and differentiate into astrocytes (Gaiano et al. 2000, Levitt et al. 1981, Pixley & de Vellis 1984, Ram´on y Cajal 1911, Schmechel & Rakic 1979, Voigt 1989).”