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Related Experiment Video

Updated: Jun 9, 2026

Method to Measure Tone of Axial and Proximal Muscle

Method to Measure Tone of Axial and Proximal Muscle

Published on: December 14, 2011

Twist1 activity thresholds define multiple functions in limb development.

Dayana Krawchuk¹, Shoshana J Weiner, You-Tzung Chen

¹Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.

Developmental Biology

|August 25, 2010

Summary

This summary is machine-generated.

Reduced Twist1 activity in limb development leads to severe skeletal defects and altered Shh signaling. This study reveals how varying Twist1 levels impact limb patterning and gene expression, offering insights into congenital limb malformations.

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Area of Science:

Developmental Biology
Genetics
Molecular Biology

Background:

The transcription factor Twist1 is crucial for limb development.
Twist1 deficiency disrupts FGF signaling and Shh expression in limb buds.
Understanding Twist1's role is key to deciphering limb malformations.

Purpose of the Study:

To investigate the impact of varying Twist1 activity levels on limb development.
To elucidate the relationship between Twist1, FGF signaling, and Shh expression.
To establish a model for Twist1-dependent limb patterning.

Main Methods:

Generation of a Twist1 allelic series (null, hypomorph, conditional alleles).
Analysis of limb skeletal defects and gene expression patterns (Shh).
Genetic manipulation of FGF targets (Etv genes) and Twist1 antagonist (Hand2).

Main Results:

Reduced Twist1 activity causes progressive skeletal defects, from polydactyly to aplasia.
Ectopic anterior Shh expression and anterior AER expansion occur with decreased Twist1.
Modulation of Etv genes and Hand2 dosage affects skeletal phenotypes.

Conclusions:

Multiple Twist1 activity thresholds regulate early limb bud patterning.
Specific limb skeletal defects correlate with distinct levels of Twist1 activity.
Twist1 dosage is critical for establishing limb structure and gene expression domains.