POLYDACTYLOUS LIMBS IN STRONGS LUXOID MICE RESULT FROM ECTOPIC POLARIZING ACTIVITY

Strong's Luxoid (lst(D)) is a semidominant mouse mutation in which het erozygotes show preaxial hindlimb polydactyly, and homozygotes show fo re- and hindlimb polydactyly. The digit patterns of these polydactylou s limbs resemble those caused by polarizing grafts, since additional d igits with posterior character are present at the anterior side of the limb. Such observations suggest that lst(D) limb buds might contain a genetically determined ectopic region of polarizing activity. Accordi ngly, we show that mutant embryos ectopically express the pattern-dete rmining genes fibroblast growth factor 4 (fgf-4), sonic hedgehog (shh) , and Hoxd-12 in the anterior region of the limb. Further, we show tha t anterior mesoderm from mutant limbs exhibits polarizing activity whe n grafted into host chicken limbs. In contrast to an experimentally de rived polydactylous transgenic mouse, forelimbs of homozygotes show a normal pattern of Hoxb-8 expression, indicating that the duplication o f polarizing tissue here occurs downstream or independently of Hoxb-8. We suggest that the lst gene product is involved in anteroposterior a xis formation during normal limb development.