POLYDACTYLY IN THE STRONGS LUXOID MOUSE IS SUPPRESSED BY LIMB DEFORMITY ALLELES

The study of limb development has provided insight into pattern format ion during vertebrate embryogenesis. Genetic approaches offer powerful ways to identify the critical molecules and their pathways of action required to execute a complex morphogenetic program. We have applied g enetic analysis to the process of limb development by studying two mou se mutants, limb deformity (ld) and Strong's luxoid (lst). These mutat ions confer contrasting phenotypic alterations to the anteroposterior limb pattern. The six mutant ld alleles are fully recessive and result in oligosyndactyly of all four limbs. By contrast, the two mutant ist alleles result in a mirror-image polydactylous limb phenotype inherit ed in a semidominant fashion. Morphological and molecular analysis of embryonic limbs has shown that the ld and lst alleles affect the exten t and distribution of two key signaling centers differentially: the ap ical ectodermal ridge and the zone of polarizing activity. Molecular c haracterization of the Id gene has defined a new family of evolutionar ily conserved proteins termed the formins. The underlying molecular de fect in the 1st mutation has not been identified; however, both loci a re tightly linked on mouse chromosome 2, suggesting the possibility th at they may be allelic. In this study, we have used genetic analysis t o examine the epistatic and allelic relationships of Id and ist. We ob served that in + ld/lst + double heterozygotes, a single mutant ld all ele is able to suppress the semi-dominant polydacious ist limb phenoty pe. By segregating the lst and ld loci in a backcross, we observed tha t these loci recombine and are separated by a genetic distance of appr oximately 6 cM. Therefore, while our observations demonstrate a geneti c interaction between ld and lst, it is probable that ld and lst are n ot allelic. Instead, lst and ld may be operating either in a linear or in a parallel (bypass) genetic pathway to affect the limb signaling c enters. (C) 1996 Wiley-Liss, Inc.