Polydactylous limbs in Strong's Luxoid mice result from ectopic polarizing activity

Area of Science:

• Developmental Biology
• Genetics
• Mouse Models

Background:

• The Strong's Luxoid (1stD) mutation in mice results in polydactyly (extra digits).
• Polydactyly in 1stD mutants resembles digit patterns induced by polarizing region grafts.
• This suggests a genetically determined ectopic polarizing activity in 1stD limb buds.

Purpose of the Study:

• To investigate the molecular mechanisms underlying limb polydactyly in Strong's Luxoid mice.
• To determine if ectopic polarizing activity is present in mutant limb buds.
• To elucidate the role of the 1st gene in anteroposterior axis formation during limb development.

Main Methods:

• Analysis of gene expression patterns (fgf-4, shh, Hoxd-12, Hoxb-8) in mutant and wild-type embryos.
• Grafting experiments using anterior mesoderm from mutant limbs into host chicken embryos.
• Phenotypic analysis of limb development in 1stD heterozygotes and homozygotes.

Main Results:

• Mutant embryos exhibit ectopic expression of fgf-4, shh, and Hoxd-12 in the anterior limb region.
• Grafts of anterior mesoderm from mutant limbs demonstrate polarizing activity.
• Forelimbs of homozygotes show normal Hoxb-8 expression, indicating downstream or independent gene duplication.

Conclusions:

• The 1stD mutation establishes an ectopic region of polarizing activity in the anterior limb.
• The 1st gene product is likely involved in establishing the anteroposterior axis during normal limb development.
• The observed polydactyly results from altered gene expression patterns downstream of or independent from Hoxb-8.