A gradient of Gli activity mediates graded Sonic Hedgehog signaling in the neural tube

被引:210
作者
Stamataki, D [1 ]
Ulloa, F [1 ]
Tsoni, SV [1 ]
Mynett, A [1 ]
Briscoe, J [1 ]
机构
[1] Natl Inst Med Res, Dept Neurobiol, London NW7 1AA, England
基金
英国医学研究理事会;
关键词
hedgehog signaling; graded morphogen signaling; neural tube development; neuronal subtype identity; vertebrate patterning mechanisms;
D O I
10.1101/gad.325905
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During development, many signaling factors behave as morphogens, long-range signals eliciting different cellular responses according to their concentration. In ventral regions of the spinal cord, Sonic Hedgehog (Shh) is such a signal and controls the emergence, in precise spatial order, of distinct neuronal subtypes. The Gli family of transcription factors plays a central role in this process. Here we demonstrate that a gradient of Gli activity is sufficient to mediate, cell-autonomously, the full range of Shh responses in the neural tube. The incremental two- to threefold changes in Shh concentration, which determine alternative neuronal subtypes, are mimicked by similar small changes in the level of Gli activity, indicating that a gradient of Gli activity represents the intracellular correlate of graded Shh signaling. Moreover, our analysis suggests that cells integrate the level of signaling over time, consistent with the idea that signal duration, in addition to signal strength, is an important parameter controlling dorsal-ventral patterning. Together, these data indicate that Shh signaling is transduced, without amplification, into a gradient of Gli activity that orchestrates patterning of the ventral neural tube.
引用
收藏
页码:626 / 641
页数:16
相关论文
共 82 条
[1]   Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning [J].
Ahn, S ;
Joyner, AL .
CELL, 2004, 118 (04) :505-516
[2]   The emergent design of the neural tube:: prepattern, SHH morphogan and GLI code [J].
Altaba, AR ;
Nguyên, V ;
Palma, V .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2003, 13 (05) :513-521
[3]   RESTRICTIONS TO FLOOR PLATE INDUCTION BY HEDGEHOG AND WINGED-HELIX GENES IN THE NEURAL-TUBE OF FROG EMBRYOS [J].
ALTABA, ARI ;
JESSEL, TM ;
ROELINK, H .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1995, 6 (02) :106-121
[4]  
Altaba ARI, 1998, DEVELOPMENT, V125, P2203
[5]   Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity [J].
Arber, S ;
Han, B ;
Mendelsohn, M ;
Smith, M ;
Jessell, TM ;
Sockanathan, S .
NEURON, 1999, 23 (04) :659-674
[6]  
Aza-Blanc P, 2000, DEVELOPMENT, V127, P4293
[7]   All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3 [J].
Bai, CB ;
Stephen, D ;
Joyner, AL .
DEVELOPMENTAL CELL, 2004, 6 (01) :103-115
[8]  
Bai CB, 2002, DEVELOPMENT, V129, P4753
[9]  
Bai CYB, 2001, DEVELOPMENT, V128, P5161
[10]  
BARTH KA, 1995, DEVELOPMENT, V121, P1755