[en] The subventricular zone (SVZ) is a source of neural progenitors throughout brain development. The identification and purification of these progenitors and the analysis of their lineage potential are fundamental issues for future brain repair therapies. We demonstrate that early postnatal NG2-expressing (NG2(+)) progenitor cells located in the SVZ self-renew in vitro and display phenotypic features of transit-amplifier type C-like multipotent cells. NG2(+) cells in the SVZ are highly proliferative and express the epidermal growth factor receptor, the transcription factors Dlx, Mash1, and Olig2, and the Lewis X (LeX) antigen. We show that grafted early postnatal NG2(+) cells generate hippocampal GABAergic interneurons that propagate action potentials and receive functional glutamatergic synaptic inputs. Our work identifies Dlx(+)/Mash1(+)/LeX(+)/NG2(+)/GFAP-negative cells of the SVZ as a new class of postnatal multipotent progenitor cells that may represent a specific cellular reservoir for renewal of postnatal and adult inhibitory interneurons in the hippocampus.
Disciplines :
Neurology
Author, co-author :
Aguirre, Adan A.
Chittajallu, Ramesh
Belachew, Shibeshih ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie
Gallo, Vittorio
Language :
English
Title :
NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus
Publication date :
24 May 2004
Journal title :
Journal of Cell Biology
ISSN :
0021-9525
eISSN :
1540-8140
Publisher :
Rockefeller Univ Press, New York, United States - New York
Alvarez-Buylla, A., and J.M. Garcia-Verdugo. 2002. Neurogenesis in adult subventricular zone. J. Neurosci. 22:629-634.
Belachew, S., R. Chittajallu, A.A. Aguirre, X. Yuan, M. Kirby, S. Anderson, and V. Gallo. 2003. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J. Cell Biol. 161:169-186.
Capela, A., and S. Temple. 2002. Lex/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron. 35:865-875.
Casaccia-Bonnefil, P., R. Tikoo, H. Kiyokawa, V. Friedrich Jr., M.V. Chao, and A. Koff. 1997. Oligodendrocyte precursor differentiation is perturbed in the absence of the cyclin-dependent kinase inhibitor p27Kip1. Genes Dev. 11:2335-2346.
Dawson, M.R., J.M. Levine, and R. Reynolds. 2000. NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J. Neurosci. Res. 61:471-479.
Desai, A.R., and S.K. McConnell. 2000. Progressive restriction in fate potential by neural progenitors during cerebral cortical development. Development. 127:2863-2872.
Doetsch, F., J.M. Garcia-Verdugo, and A. Alvarez-Buylla. 1997. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J. Neurosci, 17:5046-5061.
Doetsch, F., I. Caille, D.A. Lim, J.M. Garcia-Verdugo, and A. Alvarez-Buylla. 1999a. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 97:703-716.
Doetsch, F., J.M. Garcia-Verdugo, and A. Alvarez-Buylla. 1999b. Regeneration of a germinal layer in the adult mammalian brain. Proc. Natl. Acad. Sci. USA. 96:11619-11624.
Doetsch, F., L. Petreanu, I. Caille, J.M. Garcia-Verdugo, and A. Alvarez-Buylla. 2002a. EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron. 36:1021-1034.
Doetsch, F., J.M. Verdugo, I. Caille, A. Alvarez-Buylla, M.V. Chao, and P. Casaccia-Bonnefil. 2002b. Lack of the cell-cycle inhibitor p27Kip1 results in selective increase of transit-amplifying cells for adult neurogenesis. J. Neurosci. 22:2255-2264.
Goldman, S. 2003. Glia as neural progenitor cells. Trends Neurosci. 26:590-596.
He, W., C. Ingraham, L. Rising, S. Goderie, and S. Temple. 2001. Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis. J. Neurosci. 21:8854-8862.
Jinno, S., and T. Kosaka. 2002. Immunocytochemical characterization of hippocamposeptal projecting GABAergic nonprincipal neurons in the mouse brain: a retrograde labeling study. Brain Res. 945:219-231.
Liu, S., J. Wang, D. Zhu, Y. Fu, K. Lukowiak, and Y.M. Lu. 2003. Generation of functional inhibitory neurons in the adult rat hippocampus. J. Neurosci. 23:732-736.
Lu, Q.R., D. Yuk, J.A. Alberta, Z. Zhu, I. Pawlitzky, J. Chan, A.P. McMahon, C.D. Stiles, and D.H. Rowitch. 2000. Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system. Neuron. 25:317-329.
Ma, W., T. Behar, L. Chang, and J.L. Barker. 1994. Transient increase in expression of GAD-65 and GAD-67 mRNAs during postnatal development of rat spinal cord. J. Comp. Neurol. 346:151-160.
Marshall, C.A., and J.E. Goldman. 2002. Subpallial dlx2-expressing cells give rise to astrocytes and oligodendrocytes in the cerebral cortex and white matter. J. Neurosci. 22:9821-9830.
McBain, C.J., and A. Fisahn. 2001. Interneurons unbound. Nat. Rev. Neurosci. 2:11-23.
Nunes, M.C., N.S. Roy, H.M. Keyoung, R.R. Goodman, G. McKhann, II, L. Jiang, J. Kang, M. Nedergaard, and S.A. Goldman. 2003. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat. Med. 9:439-447.
Olsson, M., K. Campbell, and D.H. Turnbull. 1997. Specification of mouse telencephalic and mid-hindbrain progenitors following heterotopic ultrasound-guided embryonic transplantation. Neuron. 19:761-772.
Panganiban, G., and J.L. Rubenstein. 2002. Developmental functions of the Distal-less/Dlx homeobox genes. Development. 129:4371-4386.
Panganiban, G., S.M. Irvine, C. Lowe, H. Roehl, L.S. Corley, B. Sherbon, J.K. Grenier, J.F. Fallon, J. Kimble, M. Walker, et al. 1997. The origin and evolution of animal appendages. Proc. Natl. Acad. Sci. USA. 94:5162-5166.
Reynolds, B.A., and S. Weiss. 1992. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 255:1707-1710.
Schluter, C., M. Duchrow, C. Wohlenberg, M.H. Becker, G. Key, H.D. Flad, and J. Gerdes. 1993. The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins. J. Cell Biol. 123:513-522.
Stuhmer, T., S.A. Anderson, M. Ekker, and J.L. Rubensrein. 2002. Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression. Development. 129:245-252.
Suzuki, S.O., and J.E. Goldman. 2003. Multiple cell populations in the early postnatal subventricular zone take distinct migratory pathways: a dynamic study of glial and neuronal progenitor migration. J. Neurosci. 24:4240-4250.
Yuan, X., R. Chittajallu, S. Belachew, S. Anderson, C.J. McBain, and V. Gallo. 2002. Expression of the green fluorescent protein in the oligodendrocyte lineage: a transgenic mouse for developmental and physiological studies. J. Neurosci. Res. 70:529-545.
Yung, S.Y., S. Gokhan, J. Jurcsak, A.E. Molero, J.J. Abrajano, and M.F. Mehler. 2002. Differential modularion of BMP signaling promotes the elaboration of cerebral cortical GABAergic neurons or oligodendrocytes from a common sonic hedgehog-responsive ventral forebrain progenitor species. Proc. Natl. Acad. Sci. USA. 99:16273-16278.