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Related Experiment Video

Updated: Feb 11, 2026

Understanding Cerebellar Pattern Formation

Understanding Cerebellar Pattern Formation

Published on: November 1, 2007

Genetic interaction between Gli3 and Ezh2 during limb pattern formation.

Steven J Deimling¹, Kimberly Lau¹, Chi-Chung Hui²

¹Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.

Mechanisms of Development

|May 6, 2018

Summary

The study reveals Enhancer of Zeste 2 (Ezh2) is crucial for limb development by repressing hedgehog signaling. Ezh2 acts downstream of GLI3 repressor activity, suggesting Polycomb Repressive Complex 2 involvement in limb patterning.

Keywords:

Ezh2 Genetic interaction Gli3 Limb bud Mouse embryo Skeletal pattern

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Published on: January 12, 2022

Area of Science:

Developmental Biology
Genetics
Epigenetics

Background:

Limb bud anteroposterior polarity is critical for skeletal development.
GLI3 repressor activity is known to repress hedgehog signaling for anterior identity, but the mechanism is unclear.

Purpose of the Study:

To investigate the genetic interaction between Gli3 and Enhancer of Zeste 2 (Ezh2) in limb bud patterning.
To elucidate the mechanism by which hedgehog signaling is repressed during limb development.

Main Methods:

Analysis of Gli3 and conditional Ezh2 single mutant embryos.
Examination of Ezh2;Gli3 double mutant embryos.
Assessment of anterior skeletal element formation in mutant backgrounds.

Main Results:

Both Gli3 and Ezh2 loss-of-function mutants displayed loss of anterior limb identity.
The phenotype in Ezh2;Gli3 double mutants resembled Ezh2 single mutants, indicating Ezh2 is epistatic to Gli3.
Absent anterior skeletal elements in Ezh2 mutants were not rescued by manipulating Gli activator or repressor activity.

Conclusions:

Ezh2 acts epistatically to Gli3 in establishing anteroposterior limb polarity.
Hedgehog signaling repression may involve the recruitment of Polycomb Repressive Complex 2 by Ezh2.