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Limb deformity proteins: role in mesodermal induction of the apical ectodermal ridge
1Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Development (Cambridge, England)
|January 1, 1997
Summary
Mutations in limb deformity (ld) mice disrupt limb development by impairing mesenchyme-induced apical ectodermal ridge formation. This leads to shortened limbs with skeletal patterning defects due to failed fibroblast growth factor signaling.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Skeletal Biology
Background:
- Limb development relies on apical ectodermal ridge (AER) and underlying mesenchyme signaling.
- Limb deformity (ld) mutations cause severe limb shortening and patterning defects.
Purpose of the Study:
- Investigate the origin of limb patterning defects in ld mice.
- Elucidate the role of ridge-mesenchymal interactions in ld mutants.
Main Methods:
- Analysis of gene expression (Fgf8, Fgf4, Shh, Evx1, Wnt5a) in ld limbs.
- Construction of mouse-chick chimeras to assess ectoderm-mesenchyme interactions.
Main Results:
- ld mesenchyme fails to properly induce the AER.
- Decreased Fgf8 and absent Fgf4 expression in ld AER.
- Restoration of AER and normal skeletal patterning in chimeras with wild-type mesenchyme.
Conclusions:
- The ld mesenchyme is primarily defective in inducing a functional AER.
- Limb deformity protein likely acts in the AER differentiation phase, involving Fgf4 induction.
- A two-phase model for AER induction is proposed: competence (Fgf8) and differentiation (Fgf4).