|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 1 February 2006
doi: 10.1242/dev.02254
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Chemical Engineering and the Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720-1462, USA.
* Author for correspondence (e-mail: schaffer{at}cchem.berkeley.edu)
Accepted 5 December 2005
During development, secreted signaling factors, called morphogens, instruct cells to adopt specific mature phenotypes. However, the mechanisms that morphogen systems employ to establish a precise concentration gradient for patterning tissue architecture are highly complex and are typically analyzed only at long times after secretion (i.e. steady state). We have developed a theoretical model that analyzes dynamically how the intricate transport and signal transduction mechanisms of a model morphogen, Sonic hedgehog (Shh), cooperate in modular fashion to regulate tissue patterning in the neural tube. Consistent with numerous recent studies, the model elucidates how the dynamics of gradient formation can be a key determinant of cell response. In addition, this work yields several novel insights into how different transport mechanisms or `modules' control pattern formation. The model predicts that slowing the transport of a morphogen, such as by lipid modification of the ligand Shh, by ligand binding to proteoglycans, or by the moderate upregulation of dedicated transport molecules like Dispatched, can actually increase the signaling range of the morphogen by concentrating it near the secretion source. Furthermore, several transcriptional targets of Shh, such as Patched and Hedgehog-interacting protein, significantly limit its signaling range by slowing transport and promoting ligand degradation. This modeling approach elucidates how individual modular elements that operate dynamically at various times during patterning can shape a tissue pattern.
Key words: Morphogen, Sonic hedgehog, Diffusion, Transport, Modeling
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Barkai and B.-Z. Shilo Robust Generation and Decoding of Morphogen Gradients Cold Spring Harb Perspect Biol, November 1, 2009; 1(5): a001990 - a001990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Wartlick, A. Kicheva, and M. Gonzalez-Gaitan Morphogen Gradient Formation Cold Spring Harb Perspect Biol, September 1, 2009; 1(3): a001255 - a001255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yan and X. Lin Shaping Morphogen Gradients by Proteoglycans Cold Spring Harb Perspect Biol, September 1, 2009; 1(3): a002493 - a002493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Dessaud, A. P. McMahon, and J. Briscoe Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network Development, August 1, 2008; 135(15): 2489 - 2503. [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]
|
|
|
|
 |
|
 D. C. Martinelli and C.-M. Fan Gas1 extends the range of Hedgehog action by facilitating its signaling Genes & Dev., May 15, 2007; 21(10): 1231 - 1243. [Abstract] [Full Text] [PDF]
|
|
