| Abstract: | The study of limb development has provided insight into pattern formation 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 genetic analysis to the process of limb development by studying two mouse mutants, limb deformity (Id) and Strong's luxoid (Ist). These mutations confer contrasting phenotypic alterations to the anteroposterior limb pattern. The six mutant Id 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 inherited in a semidominant fashion. Morphological and molecular analysis of embryonic limbs has shown that the Id and Ist alleles affect the extent and distribution of two key signaling centers differentially: the apical ectodermal ridge and the zone of polarizing activity. Molecular characterization of the Id gene has defined a new family of evolutionarily conserved proteins termed the formins. The underlying molecular defect in the Ist mutation has not been identified; however, both loci are tightly linked on mouse chromosome 2, suggesting the possibility that they may be allelic. In this study, we have used genetic analysis to examine the epistatic and allelic relationships of Id and Ist. We observed that in + Id/Ist + double heterozygotes, a single mutant Id allele is able to suppress the semi-dominant polydactylous Ist limb phenotype. By segregating the Ist and Id loci in a backcross, we observed that these loci recombine and are separated by a genetic distance of approximately 6 cM. Therefore, while our observations demonstrate a genetic interaction between Id and Ist, it is probable that Id and Ist are not allelic. Instead, Ist and Id may be operating either in a linear or in a parallel (bypass) genetic pathway to affect the limb signaling centers. © 1996 Wiley-Liss, Inc. |
