Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus

被引:102
作者
Kunze, Albrecht [1 ,2 ]
Congreso, Marga Rubenecia [1 ]
Hartmann, Christian [1 ]
Wallraff-Beck, Anke [1 ]
Huettmann, Kerstin [1 ]
Bedner, Peter [1 ]
Requardt, Robert [3 ]
Seifert, Gerald [1 ]
Redecker, Christoph [2 ]
Willecke, Klaus [3 ]
Hofmann, Andreas [4 ]
Pfeifer, Alexander [4 ]
Theis, Martin [1 ]
Steinhaeuser, Christian [1 ]
机构
[1] Univ Bonn, Fac Med, Inst Cellular Neurosci, D-53105 Bonn, Germany
[2] Univ Jena, Hans Berger Hosp, Dept Neurol, D-07747 Jena, Germany
[3] Univ Bonn, Inst Genet, D-53117 Bonn, Germany
[4] Univ Bonn, Inst Pharmacol & Toxicol, D-53113 Bonn, Germany
关键词
adult neurogenesis; coupling; gap junction; astrocyte; patch clamp; NEURAL PROGENITOR CELLS; GAP-JUNCTIONS; DEVELOPING NEOCORTEX; HIPPOCAMPAL SLICE; MICE; ASTROCYTES; MIGRATION; PROLIFERATION; SUBPOPULATION; POPULATIONS;
D O I
10.1073/pnas.0813160106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
In the adult dentate gyrus, radial glia-like cells represent putative stem cells generating neurons and glial cells. Here, we combined patch-clamp recordings, biocytin filling, immunohistochemistry, single-cell transcript analysis, and mouse transgenics to test for connexin expression and gap junctional coupling of radial glia-like cells and its impact on neurogenesis. Radial glia-like cells were identified in mice expressing EGFP under control of the nestin and gfap promoters. We show that a majority of Radial glia-like cells are coupled and express Cx43. Neuronal precursors were not coupled. Mice lacking Cx30 and Cx43 in GFAP-positive cells displayed almost complete inhibition of proliferation and a significant decline in numbers of radial glia-like cells and granule neurons. Inducible virus-mediated ablation of connexins in the adult hippocampus also reduced neurogenesis. These findings strongly suggest the requirement of connexin expression by radial glia-like cells for intact neurogenesis in the adult brain and point to possible communication pathways of these cells.
引用
收藏
页码:11336 / 11341
页数:6
相关论文
共 39 条
[1]
Bittman K, 1997, J NEUROSCI, V17, P7037
[2]
Differential regulation of connexin 26 and 43 in murine neocortical precursors [J].
Bittman, KS ;
LoTurco, JJ .
CEREBRAL CORTEX, 1999, 9 (02) :188-195
[3]
Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus [J].
Cameron, HA ;
McKay, RDG .
JOURNAL OF COMPARATIVE NEUROLOGY, 2001, 435 (04) :406-417
[4]
Gap junctional communication is required to maintain mouse cortical neural progenitor cells in a proliferative state [J].
Cheng, AW ;
Tang, HY ;
Cai, JL ;
Zhu, M ;
Zhang, XY ;
Rao, M ;
Mattson, MP .
DEVELOPMENTAL BIOLOGY, 2004, 272 (01) :203-216
[5]
Connexin43 null mice reveal that astrocytes express multiple connexins [J].
Dermietzel, R ;
Gao, Y ;
Scemes, E ;
Vieria, D ;
Urban, M ;
Kremer, M ;
Bennett, MVL ;
Spray, DC .
BRAIN RESEARCH REVIEWS, 2000, 32 (01) :45-56
[6]
Duval N, 2002, J CELL SCI, V115, P3241
[7]
Gap junctions: Multifaceted regulators of embryonic cortical development [J].
Elias, Laura A. B. ;
Kriegstein, Arnold R. .
TRENDS IN NEUROSCIENCES, 2008, 31 (05) :243-250
[8]
Gap junction adhesion is necessary for radial migration in the neocortex [J].
Elias, Laura A. B. ;
Wang, Doris D. ;
Kriegstein, Arnold R. .
NATURE, 2007, 448 (7156) :901-U3
[9]
Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes [J].
Filippov, V ;
Kronenberg, G ;
Pivneva, T ;
Reuter, K ;
Steiner, B ;
Wang, LP ;
Yamaguchi, M ;
Kettenmann, H ;
Kempermann, G .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2003, 23 (03) :373-382
[10]
Fukuda S, 2003, J NEUROSCI, V23, P9357