|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 4 August 2004
doi: 10.1242/dev.01301
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Program in Neurobiology and Department of Pediatrics, Children's Memorial
Institute for Education and Research and The Feinberg School of Medicine,
Northwestern University, Chicago, IL 60614, USA
2 Department of Biology, University of Massachusetts, Amherst, MA 01003,
USA
** Author for correspondence (e-mail: j-kohtz{at}northwestern.edu)
Accepted 20 May 2004
The Shh protein contains both N-terminal and C-terminal lipids. The functional redundancy of these lipid moieties is presently unclear. Here, we compare the relative roles of the N- and C-terminal lipids in early rat striatal neuronal differentiation, membrane association and multimerization, and ventralizing activity in the zebrafish forebrain. We show that these lipid act synergistically in cell tethering and the formation of a large (L) multimer (669 kDa). However, the C-terminal lipid antagonizes the rat striatal neuronal differentiation-inducing activity of the N-terminal lipid. In addition, multimerization is required but not sufficient for the differentiation-inducing activity. Based on the presence of different N- and C-lipid-containing Shh proteins in the rat embryo, and on their different activities, we propose that both N- and C-terminal lipids are required for the formation of multimers involved in long-range signaling, and that the C-terminal lipid may function in long-range signaling by reducing Shh activity until it reaches its long-range target. Comparative analysis of the ventralizing activities of different N- and C-terminal lipid-containing Shh proteins in the zebrafish forebrain shows that the presence of at least one lipid is required for signaling activity, suggesting that lipid modification of Shh is a conserved requirement for signaling in the forebrain of rodents and zebrafish.
Key words: Sonic hedgehog, Lipid modifications, Forebrain
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Dierker, R. Dreier, M. Migone, S. Hamer, and K. Grobe Heparan Sulfate and Transglutaminase Activity Are Required for the Formation of Covalently Cross-linked Hedgehog Oligomers J. Biol. Chem., November 20, 2009; 284(47): 32562 - 32571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Dierker, R. Dreier, A. Petersen, C. Bordych, and K. Grobe Heparan Sulfate-modulated, Metalloprotease-mediated Sonic Hedgehog Release from Producing Cells J. Biol. Chem., March 20, 2009; 284(12): 8013 - 8022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Brill, M. Snapyan, H. Wohlfrom, J. Ninkovic, M. Jawerka, G. S. Mastick, R. Ashery-Padan, A. Saghatelyan, B. Berninger, and M. Gotz A Dlx2- and Pax6-Dependent Transcriptional Code for Periglomerular Neuron Specification in the Adult Olfactory Bulb J. Neurosci., June 18, 2008; 28(25): 6439 - 6452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Casso, S. Liu, D. D. Iwaki, S. K. Ogden, and T. B. Kornberg A Screen for Modifiers of Hedgehog Signaling in Drosophila melanogaster Identifies swm and mts Genetics, March 1, 2008; 178(3): 1399 - 1413. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Russell, R. G. Cowan, R. M. Harman, A. L. Walker, and S. M. Quirk The Hedgehog Signaling Pathway in the Mouse Ovary Biol Reprod, August 1, 2007; 77(2): 226 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Huang, Y. Litingtung, and C. Chiang Region-specific requirement for cholesterol modification of sonic hedgehog in patterning the telencephalon and spinal cord Development, June 1, 2007; 134(11): 2095 - 2105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Bijlsma, M. P. Peppelenbosch, and C. A. Spek Hedgehog Morphogen in Cardiovascular Disease Circulation, October 31, 2006; 114(18): 1985 - 1991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Feng, C. Bi, B. S. Clark, R. Mady, P. Shah, and J. D. Kohtz The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator Genes & Dev., June 1, 2006; 20(11): 1470 - 1484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Saha and D. V. Schaffer Signal dynamics in Sonic hedgehog tissue patterning Development, March 1, 2006; 133(5): 889 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Goetz, S. Singh, L. M. Suber, F. J. Kull, and D. J. Robbins A Highly Conserved Amino-terminal Region of Sonic Hedgehog Is Required for the Formation of Its Freely Diffusible Multimeric Form J. Biol. Chem., February 17, 2006; 281(7): 4087 - 4093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gallet, L. Ruel, L. Staccini-Lavenant, and P. P. Therond Cholesterol modification is necessary for controlled planar long-range activity of Hedgehog in Drosophila epithelia Development, February 1, 2006; 133(3): 407 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Horabin Splitting the Hedgehog signal: sex and patterning in Drosophila Development, November 1, 2005; 132(21): 4801 - 4810. [Abstract] [Full Text] [PDF]
|
|
