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Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning

  • 0Howard Hughes Medical Institute and Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA.
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August 19, 2004

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August 19, 2004

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Summary

This summary is machine-generated.

Sonic Hedgehog (Shh) signaling from the zone of polarizing activity (ZPA) influences vertebrate limb development. This study reveals Shh responsiveness is widespread and not a linear gradient, challenging classical morphogen models for digit identity.

Area Of Science

  • Developmental Biology
  • Molecular Biology
  • Genetics

Background

  • The zone of polarizing activity (ZPA) is crucial for vertebrate limb development, primarily through the Sonic Hedgehog (Shh) morphogen.
  • Shh signaling is understood to regulate digit identity along the anterior-posterior (A-P) axis.
  • Classical morphogen models propose stable, linear gradients of signaling molecules.

Purpose Of The Study

  • To investigate the spatial and temporal dynamics of Shh responsiveness in developing vertebrate limbs.
  • To determine if Shh signaling follows a linear gradient model in limb patterning.
  • To explore potential additional roles of Shh in limb development beyond digit specification.

Main Methods

  • Genetic marking of Shh-responding cells in mouse models.
  • Fate mapping of Shh-responsive cells in wild-type and mutant (Gli2, Gli3) limbs.
  • Analysis of Shh signaling readout over time and along the A-P axis.

Main Results

  • All posterior limb mesenchyme and ectoderm cells respond to Shh from the ZPA.
  • These Shh-responding cells contribute to posterior limb structures, including bone, muscle, and skin.
  • The integrated Shh signaling readout does not form a stable, linear gradient along the A-P axis.
  • Specific levels of positive Hedgehog (Hh) signaling are not essential for specifying digit identities, as shown in Gli2 and Gli3 mutants.

Conclusions

  • Shh responsiveness in limb development is more extensive than previously thought, encompassing both mesenchyme and ectoderm.
  • The classical linear morphogen gradient model for Shh in limb patterning is not supported by these findings.
  • Digit identity specification may rely on mechanisms independent of a precise quantitative threshold of Hh signaling.

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