Cortical Neural Precursors Inhibit Their Own Differentiation via N-Cadherin Maintenance of β-Catenin Signaling

被引:142
作者
Zhang, Jianing [1 ]
Woodhead, Gregory J. [1 ]
Swaminathan, Sruthi K. [1 ]
Noles, Stephanie R. [1 ]
McQuinn, Erin R. [1 ]
Pisarek, Anna J. [1 ]
Stocker, Adam M. [1 ]
Mutch, Christopher A. [1 ]
Funatsu, Nobuo [2 ]
Chenn, Anjen [1 ]
机构
[1] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA
[2] Univ Calif Irvine, Dept Pathol, Irvine, CA 92697 USA
关键词
CELL SELF-RENEWAL; STEM-CELLS; IN-VITRO; PATHWAY; ADHESION; POLARITY; NICHES; SIZE; REGULATOR; MOUSE;
D O I
10.1016/j.devcel.2009.12.025
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Little is known about the architecture of cellular microenvironments that support stem and precursor cells during tissue development. Although adult stem cell niches are organized by specialized supporting cells, in the developing cerebral cortex, neural stem/precursor cells reside in a neurogenic niche lacking distinct supporting cells. Here, we find that neural precursors themselves comprise the niche and regulate their own development. Precursor-precursor contact regulates beta-catenin signaling and cell fate. In vivo knockdown of N-cadherin reduces beta-catenin signaling, migration from the niche, and neuronal differentiation in vivo. N-cadherin engagement activates beta-catenin signaling via Akt, suggesting a mechanism through which cells in tissues can regulate their development. These results suggest that neural precursor cell interactions can generate a self-supportive niche to regulate their own number.
引用
收藏
页码:472 / 479
页数:8
相关论文
共 38 条
[1]   For the long run: Maintaining germinal niches in the adult brain [J].
Alvarez-Buylla, A ;
Lim, DA .
NEURON, 2004, 41 (05) :683-686
[2]   Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors [J].
Bilder, D ;
Li, M ;
Perrimon, N .
SCIENCE, 2000, 289 (5476) :113-116
[3]   The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface [J].
Cappello, Silvia ;
Attardo, Alessio ;
Wu, Xunwei ;
Iwasato, Takuji ;
Itohara, Shigeyoshi ;
Wilsch-Braeuninger, Michaela ;
Eilken, Hanna M. ;
Rieger, Michael A. ;
Schroeder, Timm T. ;
Huttner, Wieland B. ;
Brakebusch, Cord ;
Goetz, Magdalena .
NATURE NEUROSCIENCE, 2006, 9 (09) :1099-1107
[4]   Regulation of cerebral cortical size by control of cell cycle exit in neural precursors [J].
Chenn, A ;
Walsh, CA .
SCIENCE, 2002, 297 (5580) :365-369
[5]   Intrinsic polarity of mammalian neuroepithelial cells [J].
Chenn, A ;
Zhang, YA ;
Chang, BT ;
McConnell, SK .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1998, 11 (04) :183-193
[6]   Functional genomic analysis of the Wnt-Wingless signaling pathway [J].
DasGupta, R ;
Kaykas, A ;
Moon, RT ;
Perrimon, N .
SCIENCE, 2005, 308 (5723) :826-833
[7]   Critical role of N-cadherin in myofibroblast invasion and migration in vitro stimulated by colon-cancer-cell-derived TGF-β or wounding [J].
De Wever, O ;
Westbroek, W ;
Verloes, A ;
Bloemen, N ;
Bracke, M ;
Gespach, C ;
Bruyneel, E ;
Mareel, M .
JOURNAL OF CELL SCIENCE, 2004, 117 (20) :4691-4703
[8]   A transgenic Lef1/β-catenin-dependent reporter is expressed in spatially restricted domains throughout zebrafish development [J].
Dorsky, RI ;
Sheldahl, LC ;
Moon, RT .
DEVELOPMENTAL BIOLOGY, 2002, 241 (02) :229-237
[9]   Socializing with the neighbors: Stem cells and their niche [J].
Fuchs, E ;
Tumbar, T ;
Guasch, G .
CELL, 2004, 116 (06) :769-778
[10]   A COMMUNITY EFFECT IN ANIMAL DEVELOPMENT [J].
GURDON, JB .
NATURE, 1988, 336 (6201) :772-774