Abstract
The Notch pathway is essential for maintaining neural progenitor cells (NPCs) in the developing brain. Activation of the pathway is sufficient to maintain NPCs, whereas loss-of-function mutations in the critical components of the pathway cause precocious neuronal differentiation and NPC depletion. Hairy and Enhancer of split (Hes)-type transcription factors have long been thought to be the only Notch effectors for the maintenance of NPCs. Recently, a novel nuclear protein, Nepro, has been identified as another critical effector of Notch. The Notch pathway is bifurcated into Nepro and Hes-type proteins in the early development of the neocortex. The combination of Nepro and Hes-type proteins is necessary and sufficient for maintaining NPCs downstream of Notch.
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References
Molyneaux BJ, Arlotta P, Menezes JR et al. Neuronal subtype specification in the cerebral cortex. Nat Rev Neurosci 2007; 8:427–437.
Kriegstein A, Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 2009; 32:149–184.
Caviness VS, Bhide PG, Nowakowski RS. Histogenetic processes leading to the laminated neocortex: migration is only a part of the story. Dev Neurosci 2008; 30:82–95.
McConnell SK. Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation. J Neurosci 1988; 8:945–974.
Frantz GD, McConnell SK. Restriction of late cerebral cortical progenitors to an upper-layer fate. Neuron 1996; 17:55–61.
Mizutani K, Saito T. Progenitors resume generating neurons after temporary inhibition of neurogenesis by Notch activation in the mammalian cerebral cortex. Development 2005; 132:1295–1304.
Louvi A, Artavanis-Tsakonas S. Notch signaling in vertebrate neural development. Nat Rev Neurosci 2006; 7:93–102.
Gaiano N, Nye JS, Fishell G. Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 2000; 26:395–404.
Yoon KJ, Koo BK, Im SK et al. Mindbomb 1-expressing intermediate progenitors generate Notch signaling to maintain radial glial cells. Neuron 2008; 58:519–531.
Koo BK, Lim HS, Song R et al. Mind bomb 1 is essential for generating functional Notch ligands to activate Notch. Development 2005; 132:3459–3470.
Yoon K, Gaiano N. Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nat Neurosci 2005; 8:709–715.
Kageyama R, Ohtsuka T, Kobayashi T. The Hes gene family: repressors and oscillators that orchestrate embryogenesis. Development 2007; 134:1243–1251.
Ju BG, Solum D, Song EJ et al. Activating the PARP-1 sensor component of the Groucho/TLE1 corepressor complex mediates a CaMKinase IIδ-dependent neurogenic gene activation pathway. Cell 2004; 119:815–824.
Chen H, Thiagalingam A, Chopra H et al. Conservation of the Drosophila lateral inhibition pathway in human lung cancer: a hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression. Proc Natl Acad Sci USA 1997; 94:5355–5360.
Imayoshi I, Shimogori T, Ohtsuka T et al. Hes genes and neurogenin regulate nonneural versus fate specification in the dorsal telencephalic midline. Development 2008; 135:2531–2541.
Imayoshi I, Sakamoto M, Yamaguchi M et al. Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci 2010; 30:3489–3498.
Martys-Zage JL, Kim SH, Berechid B et al. Requirement for presenilin 1 in facilitating jagged 2-mediated endoproteolysis and signaling of notch 1. J Mol Neurosci 2000; 15:189–204.
Muroyama Y, Saito T. Identification of Nepro, a gene required for the maintenance of neocortex neural progenitor cells downstream of Notch. Development 2009; 136:3889–3893.
Saito T, Nakatsuji, N. Efficient gene transfer into the embryonic mouse brain using in vivo electroporation. Dev Biol 2001; 240:237–246.
Saito T. In vivo electroporation in the embryonic mouse central nervous system. Nature Protoc 2006; 1:1552–1558.
Shen Q, Wang Y, Dimos JT et al. The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells. Nature Neurosci 2006; 9:743–751.
Bray SJ. Notch signaling: a simple pathway becomes complex. Nature Rev Mol Cell Biol 2006; 7:678–689.
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Saito, T. (2012). NEPRO: A Novel Notch Effector for Maintenance of Neural Progenitor Cells in the Neocortex. In: Reichrath, J., Reichrath, S. (eds) Notch Signaling in Embryology and Cancer. Advances in Experimental Medicine and Biology, vol 727. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0899-4_5
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DOI: https://doi.org/10.1007/978-1-4614-0899-4_5
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