Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia

被引：151

作者：

Huang, Peng ^{[1
]}

Schier, Alexander F. ^{[1
]}

机构：

[1] Harvard Univ, Dept Mol & Cellular Biol, Ctr Brain Sci, Harvard Stem Cell Inst,Broad Inst, Cambridge, MA 02138 USA

来源：

DEVELOPMENT | 2009年 / 136卷 / 18期

关键词：

Cilia; Hedgehog signaling; Wnt signaling; Gli; Spinal cord; Somite; Zebrafish; INTRAFLAGELLAR TRANSPORT PROTEINS; CONVERGENT EXTENSION MOVEMENTS; PLANAR CELL POLARITY; ZINC-FINGER PROTEIN; LEFT-RIGHT AXIS; REPRESSOR FUNCTIONS; CYSTIC KIDNEY; MOUSE; ENCODES; GLI2;

D O I：

10.1242/dev.041343

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Cilia have been implicated in Hedgehog (Hh) and Wnt signaling in mouse but not in Drosophila. To determine whether the role of cilia is conserved in zebrafish, we generated maternal-zygotic (MZ) oval (ovl; ift88) mutants that lack all cilia. MZovl mutants display normal canonical and non-canonical Wnt signaling but show defects in Hh signaling. As in mouse, zebrafish cilia are required to mediate the activities of Hh, Ptc, Smo and PKA. However, in contrast to mouse Ift88 mutants, which show a dramatic reduction in Hh signaling, zebrafish MZovl mutants display dampened, but expanded, Hh pathway activity. This activity is largely due to gli1, the expression of which is fully dependent on Hh signaling in mouse but not in zebrafish. These results reveal a conserved requirement for cilia in transducing the activity of upstream regulators of Hh signaling but distinct phenotypic effects due to differential regulation and differing roles of transcriptional mediators.

引用

收藏

页码：3089 / 3098

页数：10

相关论文

共 55 条

[1] The Extracellular Domain of Smoothened Regulates Ciliary Localization and Is Required for High-Level Hh Signaling [J].

Aanstad, Pia ;

Santos, Nicole ;

Corbit, Kevin C. ;

Scherz, Paul J. ;

Trinh, Le A. ;

Salvenmoser, Willi ;

Huisken, Jan ;

Reiter, Jeremy F. ;

Stainier, Didier Y. R. .

CURRENT BIOLOGY, 2009, 19 (12) :1034-1039

[2]

Bai CB, 2002, DEVELOPMENT, V129, P4753

[3] IFT80, which encodes a conserved intraflagellar transport protein, is mutated in Jeune asphyxiating thoracic dystrophy [J].

Beales, Philip L. ;

Bland, Elizabeth ;

Tobin, Jonathan L. ;

Bacchelli, Chiara ;

Tuysuz, Beyhan ;

Hill, Josephine ;

Rix, Suzanne ;

Pearson, Chad G. ;

Kai, Masatake ;

Hartley, Jane ;

Johnson, Colin ;

Irving, Melita ;

Elcioglu, Nursel ;

Winey, Mark ;

Tada, Masazumi ;

Scambler, Peter J. .

NATURE GENETICS, 2007, 39 (06) :727-729

[4] Polaris and Polycystin-2 in dorsal forerunner cells and Kupffer's vesicle are required for specification of the zebrafish left-right axis [J].

Bisgrove, BW ;

Snarr, BS ;

Emrazian, A ;

Yost, HJ .

DEVELOPMENTAL BIOLOGY, 2005, 287 (02) :274-288

[5] The graded response to sonic hedgehog depends on cilia architecture [J].

Caspary, Tamara ;

Larkins, Christine E. ;

Anderson, Kathryn V. .

DEVELOPMENTAL CELL, 2007, 12 (05) :767-778

[6] Production of maternal-zygotic mutant zebrafish by germ-line replacement [J].

Ciruna, B ;

Weidinger, G ;

Knaut, H ;

Thisse, B ;

Thisse, C ;

Raz, E ;

Schier, AF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (23) :14919-14924

[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] Kif3a constrains β-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms [J].

Corbit, Kevin C. ;

Shyer, Amy E. ;

Dowdle, William E. ;

Gaulden, Julie ;

Singla, Veena ;

Reiter, Jeremy F. .

NATURE CELL BIOLOGY, 2008, 10 (01) :70-U54

[9] Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4 [J].

Cortellino, Salvatore ;

Wang, Chengbing ;

Wang, Baolin ;

Bassi, Maria Rosaria ;

Caretti, Elena ;

Champeval, Delphine ;

Calmont, Amelie ;

Jarnik, Michal ;

Burch, John ;

Zaret, Kenneth S. ;

Larue, Lionel ;

Bellacosa, Alfonso .

DEVELOPMENTAL BIOLOGY, 2009, 325 (01) :225-237

[10] The chicken talpid3 gene encodes a novel protein essential for Hedgehog signaling [J].

Davey, Megan G. ;

Paton, I. Robert ;

Yin, Yili ;

Schmidt, Maike ;

Bangs, Fiona K. ;

Morrice, David R. ;

Smith, Terence Gordon ;

Buxton, Paul ;

Stamataki, Despina ;

Tanaka, Mikiko ;

Muensterberg, Andrea E. ;

Briscoe, James ;

Tickle, Cheryll ;

Burt, Dave W. .

GENES & DEVELOPMENT, 2006, 20 (10) :1365-1377

← 1 2 3 4 5 6 →