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Updated: Jun 6, 2026

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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
Published on: December 14, 2015
A homeodomain feedback circuit underlies step-function interpretation of a Shh morphogen gradient during ventral
Madelen Lek1, José M Dias, Ulrika Marklund
1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Summary
Developing cells use feedback circuits to interpret morphogen gradients, not just signal concentration. This reveals how cells remember past signals for robust neural patterning.
Area of Science:
- Developmental biology
- Neuroscience
- Molecular biology
Background:
- Morphogen gradients guide cell diversity in developing tissues.
- Understanding how cells interpret subtle signal differences remains a challenge.
Purpose of the Study:
- Investigate homeodomain protein activity downstream of Sonic hedgehog (Shh) signaling.
- Elucidate feedback mechanisms in neural patterning.
Main Methods:
- Analysis of homeodomain transcription factor activity.
- Studying the Shh signaling pathway in neural development.
Main Results:
- A feedback circuit between Shh and homeodomain proteins enables non-graded regulation of Shh signaling.
- Nkx2 proteins amplify Shh responses, essential for floor plate and p3 progenitor fates.
- Pax6 antagonizes Shh signaling, limiting gradient interpretation over time.
Conclusions:
- Neural patterning relies on dynamic, non-graded cellular changes, not solely Shh concentration.
- This mechanism explains cellular memory of morphogen exposure.
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