Hippi is essential for node cilia assembly and Sonic hedgehog signaling

被引:78
作者
Houde, Caroline
Dickinson, Robin J.
Houtzager, Vicky M.
Cullum, Rebecca
Montpetit, Rachel
Metzler, Martina
Simpson, Elizabeth M.
Roy, Sophie
Hayden, Michael R.
Hoodless, Pamela A.
Nicholson, Donald W.
机构
[1] McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada
[2] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[3] Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada
[4] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada
[5] Merck Res Labs, Rahway, NJ 07065 USA
基金
加拿大健康研究院;
关键词
cilia; Hippi; Huntington disease; left-right patterning; Sonic hedgehog;
D O I
10.1016/j.ydbio.2006.09.001
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hippi functions as an adapter protein that mediates pro-apoptotic signaling from poly-glutamine-expanded huntingtin, an established cause of Huntington disease, to the extrinsic cell death pathway. To explore other functions of Hippi we generated Hippi knock-out mice. This deletion causes randomization of the embryo turning process and heart looping, which are hallmarks of defective left-right (LR) axis patterning. We report that motile monocilia normally present at the surface of the embryonic node, and proposed to initiate the break in LR symmetry, are absent on Hippi(-/-) embryos. Furthermore, defects in central nervous system development are observed. The Sonic hedgehog (Shh) pathway is downregulated in the neural tube in the absence of Hippi, which results in failure to establish ventral neural cell fate. Together, these findings demonstrate a dual role for Hippi in cilia assembly and Shh signaling during development, in addition to its proposed role in apoptosis signal transduction in the adult brain under pathogenically stressful conditions. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:523 / 533
页数:11
相关论文
共 70 条
[1]  
Altaba ARI, 1999, DEVELOPMENT, V126, P3205
[2]   HNF-3-BETA IS ESSENTIAL FOR NODE AND NOTOCHORD FORMATION IN MOUSE DEVELOPMENT [J].
ANG, SL ;
ROSSANT, J .
CELL, 1994, 78 (04) :561-574
[3]   IFT20 links kinesin II with a mammalian intraflagellar transport complex that is conserved in motile flagella and sensory cilia [J].
Baker, SA ;
Freeman, K ;
Luby-Phelps, K ;
Pazour, GJ ;
Besharse, JC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (36) :34211-34218
[4]  
Brueckner M, 2001, AM J MED GENET, V101, P339, DOI 10.1002/1096-8628(20010715)101:4<339::AID-AJMG1442>3.0.CO
[5]  
2-P
[6]   Mouse dispatched homolog1 is required for long-range, but not juxtacrine, Hh signaling [J].
Caspary, T ;
García-García, MJ ;
Huangfu, DW ;
Eggenschwiler, JT ;
Wyler, MR ;
Rakeman, AS ;
Alcorn, HL ;
Anderson, KV .
CURRENT BIOLOGY, 2002, 12 (18) :1628-1632
[7]   Vertebrate Smoothened functions at the primary cilium [J].
Corbit, KC ;
Aanstad, P ;
Singla, V ;
Norman, AR ;
Stainier, DYR ;
Reiter, JF .
NATURE, 2005, 437 (7061) :1018-1021
[8]   Role of notochord in specification of cardiac left-right orientation in zebrafish and Xenopus [J].
Danos, MC ;
Yost, HJ .
DEVELOPMENTAL BIOLOGY, 1996, 177 (01) :96-103
[9]  
Ding Q, 1998, DEVELOPMENT, V125, P2533
[10]   SONIC-HEDGEHOG, A MEMBER OF A FAMILY OF PUTATIVE SIGNALING MOLECULES, IS IMPLICATED IN THE REGULATION OF CNS POLARITY [J].
ECHELARD, Y ;
EPSTEIN, DJ ;
STJACQUES, B ;
SHEN, L ;
MOHLER, J ;
MCMAHON, JA ;
MCMAHON, AP .
CELL, 1993, 75 (07) :1417-1430