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Serrate2 is disrupted in the mouse limb-development mutant syndactylism
A Sidow1, M S Bulotsky, A W Kerrebrock
1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. arend@genome.wi.mit.edu
Nature
|October 24, 1997
Summary
The mouse syndactylism mutation reveals Serrate, a Notch ligand, is crucial for early limb development. This finding highlights the Notch pathway
Area of Science:
- Developmental biology
- Genetics
- Molecular biology
Background:
- The mouse syndactylism (sm) mutation affects early limb development, causing digit fusion.
- The apical ectodermal ridge (AER) shows hyperplasia in sm homozygotes, impacting limb bud patterning.
Purpose of the Study:
- To identify the gene responsible for the sm mutation using positional cloning.
- To elucidate the role of the Notch signaling pathway in early limb development.
Main Methods:
- Positional cloning was employed to identify the mutated gene in sm mice.
- Analysis of AER hyperplasia and its downstream effects on skeletal development.
Main Results:
- The gene mutated in sm mice was identified as encoding the Notch ligand Serrate.
- AER hyperplasia in sm mutants leads to abnormal limb bud thickening and digit fusion.
- This study distinguishes sm from syndactylies caused by later defects in cell death.
Conclusions:
- The Notch signaling pathway is essential for the earliest stages of limb bud patterning.
- The findings suggest an ancient genetic mechanism conserved between vertebrate limb development and insect wing formation.
- Three modifiers of sm were mapped, with potential candidate genes suggested.