CELLULAR ANALYSIS OF LIMB DEVELOPMENT IN THE MOUSE MUTANT HYPODACTYLY

The limb defect in the mouse Hypodactyly (Hd) affects only the distal structures. Heterozygotes (Hd/+) lack all or part of the distal phalan x and the terminal claw of digit I on the hindlimbs; mice homozygous ( Hd/Hd) for the mutation have lust one digit on each of the four limbs. Early limb development in the mutant appears normal and a change in m orphology can only be detected later. Limb buds of Hd/+ and Hd/Hd embr yos become reduced in width, with Hd/Hd buds becoming very pointed ins tead of rounded. This change in bud shape is correlated with an increa se in cell death anteriorly in Hd/+ hindlimbs and both anteriorly and posteriorly in Hd/Hd fore- and hindlimb buds. The apical ectodermal ri dge is very pronounced in pointed Hd/Hd limb buds. Mesenchyme cells fr om the Hd/Hd mutant in culture show a cell-autonomous change in behavi our and less cartilage differentiates. (C) 1996 Wiley-Liss, Inc.