A genetic screen in Drosophila for identifying novel components of the Hedgehog signaling pathway

被引:32
作者
Collins, RT [1 ]
Cohen, SM [1 ]
机构
[1] European Mol Biol Lab, Dev Biol Programme, D-69117 Heidelberg, Germany
关键词
D O I
10.1534/genetics.104.039420
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The Hedgehog signaling pathway plays an essential role in the pattern formation and development of metazoan animals. Misregulation of Hedgehog signaling has also been associated with the formation of multiple types of cancer. For these reasons, the Hedgehog pathway has attracted considerable interest. Many proteins required in the Hedgehog pathway have been identified, and while much has been learned about their function in signal transduction, it is clear that this complement of proteins does not comprise the full set necessary for Hedgehog signal transduction. Because significant gaps remain in our knowledge of the molecules required for Hedgehog signaling, we performed an enhancer/suppressor screen in DrosoPhila melanogaster to identify novel components of the pathway. In addition to the isolation of new alleles of the known pathway components patched and smoothened, this screen identified 14 novel complementation groups and a larger number of loci represented by single alleles. These groups include mutations in the genes encoding the translation factors eRF1 and eIFIA and the kinesin-like protein Pavarotti. It also identified mutations in a gene whose product is necessary for the movement of Hedgehog protein through tissues.
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页码:173 / 184
页数:12
相关论文
共 78 条
[1]  
Abdelilah-Seyfried S, 2001, GENETICS, V157, P457
[2]   pavarotti encodes a kinesin-like protein required to organize the central spindle and contractile ring for cytokinesis [J].
Adams, RR ;
Tavares, AAM ;
Salzberg, A ;
Bellen, HJ ;
Glover, DM .
GENES & DEVELOPMENT, 1998, 12 (10) :1483-1494
[3]   Posttranscriptional regulation of smoothened is part of a self-correcting mechanism in the hedgehog signaling system [J].
Alcedo, J ;
Zou, Y ;
Noll, M .
MOLECULAR CELL, 2000, 6 (02) :457-465
[4]   The Drosophila smoothened gene encodes a seven-pass membrane protein, a putative receptor for the hedgehog signal [J].
Alcedo, J ;
Ayzenzon, M ;
VonOhlen, T ;
Noll, M ;
Hooper, JE .
CELL, 1996, 86 (02) :221-232
[5]   Gli and hedgehog in cancer:: Tumours, embryos and stem cells [J].
Altaba, AR ;
Sánchez, P ;
Dahmane, N .
NATURE REVIEWS CANCER, 2002, 2 (05) :361-372
[6]   Proteolysis that is inhibited by Hedgehog targets Cubitus interruptus protein to the nucleus and converts it to a repressor [J].
AzaBlanc, P ;
RamirezWeber, FA ;
Laget, MP ;
Schwartz, C ;
Kornberg, TB .
CELL, 1997, 89 (07) :1043-1053
[7]   Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours [J].
Berman, DM ;
Karhadkar, SS ;
Maitra, A ;
de Oca, RM ;
Gerstenblith, MR ;
Briggs, K ;
Parker, AR ;
Shimada, Y ;
Eshleman, JR ;
Watkins, DN ;
Beachy, PA .
NATURE, 2003, 425 (6960) :846-851
[8]  
BRIZUELA BJ, 1994, GENETICS, V137, P803
[9]   Hedgehog signaling and the axial patterning of Drosophila wings [J].
Brook, WJ .
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE, 2000, 78 (05) :585-591
[10]  
BUMCROT DA, 1995, MOL CELL BIOL, V15, P2294