EphB receptors coordinate migrationand proliferation in the intestinal stem cell niche

被引:253
作者
Holmberg, Johan [1 ]
Genander, Maria
Halford, Michael M.
Anneren, Cecilia
Sondell, Mariann
Chumley, Michael J.
Silvany, Robert E.
Henkemeyer, Mark
Frisen, Jonas
机构
[1] Karolinska Inst, Med Nobel Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden
[2] Univ Texas, SW Med Ctr, Ctr Dev Biol, Dallas, TX 75390 USA
关键词
D O I
10.1016/j.cell.2006.04.030
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
More than 10(10) cells are generated every day in the human intestine. Wnt proteins are key regulators of proliferation and are known endogenous mitogens for intestinal progenitor cells. The positioning of cells within the stem cell niche in the intestinal epithelium is controlled by B subclass ephrins through their interaction with EphB receptors. We report that EphB receptors, in addition to directing cell migration, regulate proliferation in the intestine. EphB signaling promotes cell-cycle reentry of progenitor cells and accounts for approximately 50% of the mitogenic activity in the adult mouse small intestine and colon. These data establish EphB receptors as key coordinators of migration and proliferation in the intestinal stem cell niche.
引用
收藏
页码:1151 / 1163
页数:13
相关论文
共 51 条
[11]   Socializing with the neighbors: Stem cells and their niche [J].
Fuchs, E ;
Tumbar, T ;
Guasch, G .
CELL, 2004, 116 (06) :769-778
[12]   Examining the role of Paneth cells in the small intestine by lineage ablation in transgenic mice [J].
Garabedian, EM ;
Roberts, LJJ ;
McNevin, MS ;
Gordon, JI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (38) :23729-23740
[13]   Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumours [J].
Guo, DL ;
Zhang, J ;
Yuen, ST ;
Tsui, WY ;
Chan, ASY ;
Ho, C ;
Ji, JF ;
Leung, SY ;
Chen, X .
CARCINOGENESIS, 2006, 27 (03) :454-464
[14]   De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine [J].
Haramis, APG ;
Begthel, H ;
van den Born, M ;
van Es, J ;
Jonkheer, S ;
Offerhaus, GJA ;
Clevers, H .
SCIENCE, 2004, 303 (5664) :1684-1686
[15]   BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-β-catenin signaling [J].
He, XC ;
Zhang, JW ;
Tong, WG ;
Tawfik, O ;
Ross, J ;
Scoville, DH ;
Tian, Q ;
Zeng, X ;
He, X ;
Wiedemann, LM ;
Mishina, Y ;
Li, LH .
NATURE GENETICS, 2004, 36 (10) :1117-1121
[16]  
Hearn CJ, 1999, DEV DYNAM, V214, P239, DOI 10.1002/(SICI)1097-0177(199903)214:3<239::AID-AJA7>3.0.CO
[17]  
2-O
[18]   Nuk controls pathfinding of commissural axons in the mammalian central nervous system [J].
Henkemeyer, M ;
Orioli, D ;
Henderson, JT ;
Saxton, TM ;
Roder, J ;
Pawson, T ;
Klein, R .
CELL, 1996, 86 (01) :35-46
[19]   Regulation of repulsion versus adhesion by different splice forms of an Eph receptor [J].
Holmberg, J ;
Clarke, DL ;
Frisén, J .
NATURE, 2000, 408 (6809) :203-206
[20]   Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis [J].
Holmberg, J ;
Armulik, A ;
Senti, KA ;
Edoff, K ;
Spalding, K ;
Momma, S ;
Cassidy, R ;
Flanagan, JG ;
Frisén, J .
GENES & DEVELOPMENT, 2005, 19 (04) :462-471