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Cited by 211Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationCongenital heart defects research

Notch1 control of oligodendrocyte differentiation in the spinal cord

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Genoud, Stéphane, Lappe-Siefke, Corinna, Goebbels, Sandra, Radtke, Freddy, Aguet, Michel, Scherer, Steven S., Suter, Ueli, Nave, Klaus-Armin +1 more·2002·The Journal of Cell Biology
DOI 10.1083/jcb.200202002PMC PMC2174019
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Abstract

We have selectively inhibited Notch1 signaling in oligodendrocyte precursors (OPCs) using the Cre/loxP system in transgenic mice to investigate the role of Notch1 in oligodendrocyte (OL) development and differentiation. Early development of OPCs appeared normal in the spinal cord. However, at embryonic day 17.5, premature OL differentiation was observed and ectopic immature OLs were present in the gray matter. At birth, OL apoptosis was strongly increased in Notch1 mutant animals. Premature OL differentiation was also observed in the cerebrum, indicating that Notch1 is required for the correct spatial and temporal regulation of OL differentiation in various regions of the central nervous system. These findings establish a widespread function of Notch1 in the late steps of mammalian OPC development in vivo.

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  • Cnp Cre mice also recombine Schwann cells and off-target in subsets of CNS neurons including motoneuronal precursors.

    “However, Cnp Cre mice also recombine Schwann cells and off-target in subsets of CNS neurons including motoneuronal precursors (Genoud et al., 2002;Jo et al., 2021;Tognatta et al., 2017) (Figure S1a-e).”

    From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Genoud et al., 2002

    The Results (Fig. 1) report Cnp-Cre recombination in the developing spinal cord’s ventral horns, presumably in motoneurons, and the Discussion describes Cre expression in early oligodendrocyte progenitors and motoneurons. Our copy does not report recombination in Schwann cells; the Fig. 1 caption identifies nearby nerve roots and dorsal root ganglia as PNS structures but does not establish Schwann-cell recombination. (LLM, conf=0.87)

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  1. Apelqvist, A., H. Li, L. Sommer, P. Beatus, D.J. Anderson, T. Honjo, M. Hrabe de Angelis, U. Lendahl, and H. Edlund. 1999. Notch signalling controls pancreatic cell differentiation. Nature. 400: 877–881. 10476967
  2. Armstrong, R.C., H.H. Dorn, C.V. Kufta, E. Friedman, and M.E. Dubois-Dalcq. 1992. Pre-oligodendrocytes from adult human CNS. J. Neurosci. 12: 1538–1547. 1556607 PMC6575800
  3. Artavanis-Tsakonas, S., K. Matsuno, and M.E. Fortini. 1995. Notch signaling. Science. 268: 225–232. 7716513
  4. Artavanis-Tsakonas, S., M.D. Rand, and R.J. Lake. 1999. Notch signaling: cell fate control and signal integration in development. Science. 284: 770–776. 10221902
  5. Barres, B.A., and M.C. Raff. 1993. Proliferation of oligodendrocyte precursor cells depends on electrical activity in axons. Nature. 361: 258–260. 8093806
  6. Barres, B.A., and M.C. Raff. 1994. Control of oligodendrocyte number in the developing rat optic nerve. Neuron. 12: 935–942. 8185952
  7. Barres, B.A., I.K. Hart, H.S. Coles, J.F. Burne, J.T. Voyvodic, W.D. Richardson, and M.C. Raff. 1992. Cell death in the oligodendrocyte lineage. J. Neurobiol. 23: 1221–1230. 1469385
  8. Barres, B.A., M.A. Lazar, and M.C. Raff. 1994. A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development. 120: 1097–1108. 8026323
  9. Berezovska, O., P. McLean, R. Knowles, M. Frosh, F.M. Lu, S.E. Lux, and B.T. Hyman. 1999. Notch1 inhibits neurite outgrowth in postmitotic primary neurons. Neuroscience. 93: 433–439. 10465425
  10. Blaschuk, K.L., and C. ffrench-Constant. 1998. Developmental neurobiology: notch is tops in the developing brain. Curr. Biol. 8: R334–R337. 9601631
  11. Calver, A.R., A.C. Hall, W.P. Yu, F.S. Walsh, J.K. Heath, C. Betsholtz, and W.D. Richardson. 1998. Oligodendrocyte population dynamics and the role of PDGF in vivo. Neuron. 20: 869–882. 9620692
  12. Casaccia-Bonnefil, P. 2000. Cell death in the oligodendrocyte lineage: a molecular perspective of life/death decisions in development and disease. Glia. 29: 124–135. 10625330
  13. Chambers, C.B., Y. Peng, H. Nguyen, N. Gaiano, G. Fishell, and J.S. Nye. 2001. Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors. Development. 128: 689–702. 11171394
  14. Chandross, K.J., R.I. Cohen, P. Paras, Jr., M. Gravel, P.E. Braun, and L.D. Hudson. 1999. Identification and characterization of early glial progenitors using a transgenic selection strategy. J. Neurosci. 19: 759–774. 9880596 PMC6782214
  15. Conlon, R.A., A.G. Reaume, and J. Rossant. 1995. Notch1 is required for the coordinate segmentation of somites. Development. 121: 1533–1545. 7789282
  16. Demerens, C., B. Stankoff, M. Logak, P. Anglade, B. Allinquant, F. Couraud, B. Zalc, and C. Lubetzki. 1996. Induction of myelination in the central nervous system by electrical activity. Proc. Natl. Acad. Sci. USA. 93: 9887–9892. 8790426 PMC38524
  17. Durand, B., and M. Raff. 2000. A cell-intrinsic timer that operates during oligodendrocyte development. Bioessays. 22: 64–71. 10649292
  18. Franklin, J.L., B.E. Berechid, F.B. Cutting, A. Presente, C.B. Chambers, D.R. Foltz, A. Ferreira, and J.S. Nye. 1999. Autonomous and non-autonomous regulation of mammalian neurite development by Notch1 and Delta1. Curr. Biol. 9: 1448–1457. 10607588
  19. Fu, H., Y. Qi, M. Tan, J. Cai, H. Takebayashi, M. Nakafuku, W. Richardson, and M. Qiu. 2002. Dual origin of spinal oligodendrocyte progenitors and evidence for the cooperative role of Olig2 and Nkx2.2 in the control of oligodendrocyte differentiation. Development. 129: 681–693. 11830569
  20. Furukawa, T., S. Mukherjee, Z.Z. Bao, E.M. Morrow, and C.L. Cepko. 2000. rax, Hes1, and notch1 promote the formation of Müller glia by postnatal retinal progenitor cells. Neuron. 26: 383–394. 10839357
  21. Gaiano, N., J.S. Nye, and G. Fishell. 2000. Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron. 26: 395–404. 10839358
  22. Gao, F.B., J. Apperly, and M. Raff. 1998. Cell-intrinsic timers and thyroid hormone regulate the probability of cell-cycle withdrawal and differentiation of oligodendrocyte precursor cells. Dev. Biol. 197: 54–66. 9578618
  23. Gard, A.L., and S.E. Pfeiffer. 1990. Two proliferative stages of the oligodendrocyte lineage (A2B5+O4− and O4+GalC−) under different mitogenic control. Neuron. 5:615–625. 2223090
  24. Gavrieli, Y., Y. Sherman, and S.A. Ben-Sasson. 1992. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol. 119: 493–501. 1400587 PMC2289665
  25. Givogri, M.I., R.M. Costa, V. Schonmann, A.J. Silva, A.T. Campagnoni, and E.R. Bongarzone. 2002. Central nervous system myelination in mice with deficient expression of Notch1 receptor. J. Neurosci. Res. 67: 309–320. 11813235
  26. Gravel, M., A. Di Polo, P.B. Valera, and P.E. Braun. 1998. Four-kilobase sequence of the mouse CNP gene directs spatial and temporal expression of lacZ in transgenic mice. J. Neurosci. Res. 53: 393–404. 9710259
  27. Hardy, R., and R. Reynolds. 1991. Proliferation and differentiation potential of rat forebrain oligodendroglial progenitors both in vitro and in vivo. Development. 111: 1061–1080. 1879350
  28. Hardy, R.J., and V.L. Friedrich, Jr. 1996. Oligodendrocyte progenitors are generated throughout the embryonic mouse brain, but differentiate in restricted foci. Development. 122: 2059–2069. 8681787
  29. Irvin, D.K., S.D. Zurcher, T. Nguyen, G. Weinmaster, and H.I. Kornblum. 2001. Expression patterns of Notch1, Notch2, and Notch3 suggest multiple functional roles for the Notch-DSL signaling system during brain development. J. Comp. Neurol. 436: 167–181. 11438922
  30. Ito, T., N. Udaka, T. Yazawa, K. Okudela, H. Hayashi, T. Sudo, F. Guillemot, R. Kageyama, and H. Kitamura. 2000. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Development. 127: 3913–3921. 10952889
  31. Jordan, C., V. Friedrich, Jr., and M. Dubois-Dalcq. 1989. In situ hybridization analysis of myelin gene transcripts in developing mouse spinal cord. J. Neurosci. 9: 248–257. 2464047 PMC6570014
  32. Kondo, T., and M. Raff. 2000a. Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation. Development. 127: 2989–2998. 10862737
  33. Kondo, T., and M. Raff. 2000b. The Id4 HLH protein and the timing of oligodendrocyte differentiation. EMBO J. 19: 1998–2007. 10790366 PMC305683
  34. Lindsell, C.E., J. Boulter, G. diSibio, A. Gossler, and G. Weinmaster. 1996. Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand-receptor pairs that may function in neural development. Mol. Cell. Neurosci. 8: 14–27. 8923452
  35. Lu, Q.R., L. Cai, D. Rowitch, C.L. Cepko, and C.D. Stiles. 2001. Ectopic expression of Olig1 promotes oligodendrocyte formation and reduces neuronal survival in developing mouse cortex. Nat. Neurosci. 4: 973–974. 11574831
  36. Lu, Q.R., T. Sun, Z. Zhu, N. Ma, M. Garcia, C.D. Stiles, and D.H. Rowitch. 2002. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell. 109: 75–86. 11955448
  37. Lütolf, S., F. Radtke, M. Aguet, U. Suter, and V. Taylor. 2002. Notch1 is required for neuronal and glial differentiation in the cerebellum. Development. 129: 373–385. 11807030
  38. McLaughlin, K.A., M.S. Rones, and M. Mercola. 2000. Notch regulates cell fate in the developing pronephros. Dev. Biol. 227: 567–580. 11071775
  39. Miller, R.H. 1996. Oligodendrocyte origins. Trends Neurosci. 19: 92–96. 9054062
  40. Miller, R.H., J. Payne, L. Milner, H. Zhang, and D.M. Orentas. 1997. Spinal cord oligodendrocytes develop from a limited number of migratory highly proliferative precursors. J. Neurosci. Res. 50: 157–168. 9373026
  41. Milner, R., and C. Ffrench-Constant. 1994. A developmental analysis of oligodendroglial integrins in primary cells: changes in alpha v-associated beta subunits during differentiation. Development. 120: 3497–3506. 7821217
  42. Morrison, S.J., S.E. Perez, Z. Qiao, J.M. Verdi, C. Hicks, G. Weinmaster, and D.J. Anderson. 2000. Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell. 101: 499–510. 10850492
  43. Nijjar, S.S., H.A. Crosby, L. Wallace, S.G. Hubscher, and A.J. Strain. 2001. Notch receptor expression in adult human liver: a possible role in bile duct formation and hepatic neovascularization. Hepatology. 34: 1184–1192. 11732008
  44. Noll, E., and R.H. Miller. 1993. Oligodendrocyte precursors originate at the ventral ventricular zone dorsal to the ventral midline region in the embryonic rat spinal cord. Development. 118: 563–573. 8223279
  45. Pfaff, S.L., M. Mendelsohn, C.L. Stewart, T. Edlund, and T.M. Jessell. 1996. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Cell. 84: 309–320. 8565076
  46. Pringle, N.P., and W.D. Richardson. 1993. A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage. Development. 117: 525–533. 8330523
  47. Qi, Y., J. Cai, Y. Wu, R. Wu, J. Lee, H. Fu, M. Rao, L. Sussel, J. Rubenstein, and M. Qiu. 2001. Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development. 128: 2723–2733. 11526078
  48. Radtke, F., A. Wilson, G. Stark, M. Bauer, J. van Meerwijk, H.R. MacDonald, and M. Aguet. 1999. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity. 10: 547–558. 10367900
  49. Raff, M.C., B. Durand, and F.B. Gao. 1998. Cell number control and timing in animal development: the oligodendrocyte cell lineage. Int. J. Dev. Biol. 42: 263–267. 9654007
  50. Rechsteiner, M., and S.W. Rogers. 1996. PEST sequences and regulation by proteolysis. Trends Biochem. Sci. 21: 267–271. 8755249
  51. Redmond, L., S.R. Oh, C. Hicks, G. Weinmaster, and A. Ghosh. 2000. Nuclear Notch1 signaling and the regulation of dendritic development. Nat. Neurosci. 3: 30–40. 10607392
  52. Richardson, W.D., N.P. Pringle, W.P. Yu, and A.C. Hall. 1997. Origins of spinal cord oligodendrocytes: possible developmental and evolutionary relationships with motor neurons. Dev. Neurosci. 19: 58–68. 9078434
  53. Richardson, W.D., H.K. Smith, T. Sun, N.P. Pringle, A. Hall, and R. Woodruff. 2000. Oligodendrocyte lineage and the motor neuron connection. Glia. 29: 136–142. 10625331
  54. Robey, E. 1997. Notch in vertebrates. Curr. Opin. Genet. Dev. 7: 551–557. 9309189
  55. Rogister, B., T. Ben-Hur, and M. Dubois-Dalcq. 1999. From neural stem cells to myelinating oligodendrocytes. Mol. Cell. Neurosci. 14: 287–300. 10588385
  56. Sestan, N., S. Artavanis-Tsakonas, and P. Rakic. 1999. Contact-dependent inhibition of cortical neurite growth mediated by notch signaling. Science. 286: 741–746. 10531053
  57. Solanky, M., Y. Maeda, X. Ming, W. Husar, W. Li, S. Cook, and P. Dowling. 2001. Proliferating oligodendrocytes are present in both active and chronic inactive multiple sclerosis plaques. J. Neurosci. Res. 65: 308–317. 11494366
  58. Soriano, P. 1999. Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat. Genet. 21: 70–71. 9916792
  59. Spassky, N., C. Goujet-Zalc, E. Parmantier, C. Olivier, S. Martinez, A. Ivanova, K. Ikenaka, W. Macklin, I. Cerruti, B. Zalc, and J.L. Thomas. 1998. Multiple restricted origin of oligodendrocytes. J. Neurosci. 18: 8331–8343. 9763477 PMC6792828
  60. Spassky, N., C. Olivier, E. Perez-Villegas, C. Goujet-Zalc, S. Martinez, J. Thomas, and B. Zalc. 2000. Single or multiple oligodendroglial lineages: a controversy. Glia. 29: 143–148. 10625332
  61. Sun, T., N.P. Pringle, A.P. Hardy, W.D. Richardson, and H.K. Smith. 1998. Pax6 influences the time and site of origin of glial precursors in the ventral neural tube. Mol. Cell. Neurosci. 12: 228–239. 9828088
  62. Swiatek, P.J., C.E. Lindsell, F.F. del Amo, G. Weinmaster, and T. Gridley. 1994. Notch1 is essential for postimplantation development in mice. Genes Dev. 8: 707–719. 7926761
  63. Tanigaki, K., F. Nogaki, J. Takahashi, K. Tashiro, H. Kurooka, and T. Honjo. 2001. Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate. Neuron. 29: 45–55. 11182080
  64. Temple, S., and M.C. Raff. 1986. Clonal analysis of oligodendrocyte development in culture: evidence for a developmental clock that counts cell divisions. Cell. 44: 773–779. 3948247
  65. Timsit, S., S. Martinez, B. Allinquant, F. Peyron, L. Puelles, and B. Zalc. 1995. Oligodendrocytes originate in a restricted zone of the embryonic ventral neural tube defined by DM-20 mRNA expression. J. Neurosci. 15: 1012–1024. 7869079 PMC6577809
  66. Tsuchida, T., M. Ensini, S.B. Morton, M. Baldassare, T. Edlund, T.M. Jessell, and S.L. Pfaff. 1994. Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes. Cell. 79: 957–970. 7528105
  67. van Heyningen, P., A.R. Calver, and W.D. Richardson. 2001. Control of progenitor cell number by mitogen supply and demand. Curr. Biol. 11: 232–241. 11250151
  68. Wakamatsu, Y., T.M. Maynard, and J.A. Weston. 2000. Fate determination of neural crest cells by NOTCH-mediated lateral inhibition and asymmetrical cell division during gangliogenesis. Development. 127: 2811–2821. 10851127
  69. Wang, S., A.D. Sdrulla, G. diSibio, G. Bush, D. Nofziger, C. Hicks, G. Weinmaster, and B.A. Barres. 1998. Notch receptor activation inhibits oligodendrocyte differentiation. Neuron. 21: 63–75. 9697852
  70. Wang, S., A. Sdrulla, J.E. Johnson, Y. Yokota, and B.A. Barres. 2001. A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development. Neuron. 29: 603–614. 11301021
  71. Weinmaster, G. 1998. Notch signaling: direct or what? Curr. Opin. Genet. Dev. 8: 436–442. 9729720
  72. Wolfer, A., T. Bakker, A. Wilson, M. Nicolas, V. Ioannidis, D.R. Littman, P.P. Lee, C.B. Wilson, W. Held, H.R. MacDonald, and F. Radtke. 2001. Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development. Nat. Immunol. 2: 235–241. 11224523
  73. Yu, W.P., E.J. Collarini, N.P. Pringle, and W.D. Richardson. 1994. Embryonic expression of myelin genes: evidence for a focal source of oligodendrocyte precursors in the ventricular zone of the neural tube. Neuron. 12: 1353–1362. 7516688
  74. Zhang, H., and R.H. Miller. 1996. Density-dependent feedback inhibition of oligodendrocyte precursor expansion. J. Neurosci. 16: 6886–6895. 8824327 PMC6579258
  75. Zhou, Q., G. Choi, and D.J. Anderson. 2001. The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2. Neuron. 31: 791–807. 11567617

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Authors
Genoud, S., Lappe-Siefke, C., Goebbels, S., Radtke, F., Aguet, M., Scherer, S. S., Suter, U., Nave, K.-A., & Mantei, N.
Affiliations
  • 1Department of Biology, Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland
  • Max Planck Institute of Experimental Medicine (DE)
  • University of Lausanne (CH)
  • 3Swiss Institute of Experimental Cancer Research, CH-1066 Epalinges, Switzerland
  • University of Pennsylvania (US)
  • ETH Zurich (CH)
Corresponding author
Mantei, Ned
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2002-08-19
Volume
158
Issue
4
Pages
709-718
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.200202002
PMC
PMC2174019
OpenAlex
W2044269722
Cited by
211
References
2
Citations by year
2026: 7 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 10 · 2021: 9 · 2020: 11 · 2019: 9 · 2018: 5 · 2017: 11 · 2016: 5 · 2015: 8 · 2014: 8 · 2013: 16 · 2012: 7
FWCI
1.73
Type
journal article
Language
en
Open access
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • SERVAL (Université de Lausanne) (submittedVersion, other-oa)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
Keywords
Notch1 signaling, oligodendrocyte differentiation, oligodendrocyte precursor cells, spinal cord, premature differentiation, oligodendrocyte apoptosis, Cre-loxP conditional knockout, gray matter, cerebrum, central nervous system development
MeSH terms
Animals, Cell Differentiation, Membrane Proteins, Mice, Transgenic, Mutation, Oligodendroglia, Receptors, Cell Surface, Spinal Cord, Transcription Factors, Prosencephalon, Apoptosis, Mice, Receptor, Notch1

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