Differential requirement for Gli2 and Gli3 in ventral neural cell fate specification

被引:83
作者
Motoyama, J
Milenkovic, L
Iwama, M
Shikata, Y
Scott, MP
Hui, CC
机构
[1] Univ Toronto, Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada
[2] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1X8, Canada
[3] RIKEN, Brain Res Inst, Mol Neuropathol Grp, Wako, Saitama 3510198, Japan
[4] Stanford Univ, Sch Med, Howard Hughes Med Inst, Beckman Ctr B300,Dept Dev Biol, Stanford, CA 94305 USA
[5] Stanford Univ, Sch Med, Howard Hughes Med Inst, Beckman Ctr B300,Dept Genet, Stanford, CA 94305 USA
基金
加拿大健康研究院;
关键词
mouse embryo; mutant; neural tube; ventral cell fates; Shh; Ptc1; Gli2; Gli3; rostral-caudal axis;
D O I
10.1016/S0012-1606(03)00159-3
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Sonic hedgehog (Shh) directs the development of ventral cell fates, including floor plate and V3 interneurons, in the mouse neural tube. Here, we show that the transcription factors Gli2 and Gli3, mediators of Shh signaling, are required for the development of the ventral cell fates but make distinct contributions to controlling cell fates at different locations along the rostral-caudal axis. Mutants lacking Patched1 (Ptc1), the putative receptor of Shh, were used to analyze Gli functions. Ptc1(-/-) mutants develop floor plate, motor neuron, and V3 interneuron progenitors in lateral and dorsal regions, suggesting that the normal role of Ptc1 is to suppress ventral cell development in dorsal neural tube. The Ptc1(-/-) phenotype is rescued, with restoration of dorsal cell types, by the lack of Gli2, but only in the caudal neural tube. In triple mutants of Gli2, Gli3, and Ptc1, dorsal and lateral cell fates are restored in the entire neural tube. These observations suggest that Gli2 is essential for ventral specification in the caudal neural tube, and that in more rostral regions, only Gli3 can promote development of ventral cells if Gli2 is absent. Thus, Shh signaling is mediated by overlapping but distinct functions of Gli2 and Gli3, and their relative contributions vary along the rostral-caudal axis. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:150 / 161
页数:12
相关论文
共 48 条
[1]   Gli proteins and Hedgehog signaling - development and cancer [J].
Altaba, ARI .
TRENDS IN GENETICS, 1999, 15 (10) :418-425
[2]   Mouse GLI3 regulates Fgf8 expression and apoptosis in the developing neural tube, face, and limb bud [J].
Aoto, K ;
Nishimura, T ;
Eto, K ;
Motoyame, J .
DEVELOPMENTAL BIOLOGY, 2002, 251 (02) :320-332
[3]  
Aza-Blanc P, 2000, DEVELOPMENT, V127, P4293
[4]   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
[5]  
Bai CB, 2002, DEVELOPMENT, V129, P4753
[6]   A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of Sonic hedgehog in the neural tube [J].
Briscoe, J ;
Chen, Y ;
Jessell, TM ;
Struhl, G .
MOLECULAR CELL, 2001, 7 (06) :1279-1291
[7]   The XtJ allele generates a Gli3 fusion transcript [J].
Büscher, D ;
Grotewold, L ;
Rüther, U .
MAMMALIAN GENOME, 1998, 9 (08) :676-678
[8]   Dual roles for patched in sequestering and transducing hedgehog [J].
Chen, Y ;
Struhl, G .
CELL, 1996, 87 (03) :553-563
[9]   Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function [J].
Chiang, C ;
Ying, LTT ;
Lee, E ;
Young, KE ;
Corden, JL ;
Westphal, H ;
Beachy, PA .
NATURE, 1996, 383 (6599) :407-413
[10]   Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein [J].
Chuang, PT ;
McMahon, AP .
NATURE, 1999, 397 (6720) :617-621