Related Experiment Videos
Short- and long-range effects of Sonic hedgehog in limb development
Robert Dillon1, Chetan Gadgil, Hans G Othmer
1Department of Mathematics, Washington State University, Pullman, WA 99164, USA. dillon@math.wsu.edu
Summary
Sonic hedgehog (Shh) acts as a long-range morphogen in vertebrate limb development. A new model explains how Shh signaling, involving Patched (Ptc) and Smoothened (Smo), functions across different distances.
Area of Science:
- Developmental biology
- Molecular signaling
- Biophysics
Background:
- Sonic hedgehog (Shh) and Patched (Ptc) are crucial for vertebrate limb development.
- The precise mechanism and range of Shh signaling remain unclear.
- Shh's role as a morphogen at the microm scale is debated due to transport challenges.
Purpose of the Study:
- To develop a model investigating the transport and signaling of two experimental Shh forms.
- To propose a two-state model for the Patched-Smoothened (Ptc-Smo) interaction.
- To reconcile experimental findings regarding Shh transport and signaling range.
Main Methods:
- Computational modeling of Shh signal transduction.
- Analysis of a two-state Ptc-Smo interaction model.
- Comparison with experimental data from bead and tissue implants.
Main Results:
- The model explains experimental results without assuming different Shh diffusivities.
- Variations in Shh release rates adequately explain observed phenomena.
- Lower Shh concentrations in beads mimic tissue transplant responses.
Conclusions:
- Shh can function as a long-range morphogen in limb development.
- A unified signal transduction mechanism explains both short- and long-range Shh effects.
- The Ptc-Smo interaction model provides a framework for understanding Shh signaling dynamics.