The long range goals of the proposed research are to better define the developmental and genetic pathways of limb development and the left-right asymmetry determination in mammals. The investigators propose to take advantage of lgl mutant mice in this effort. They propose to study the altered gene expression patterns in lgl mutants to better define the mesenchymal ectodermal interactions required for apical ectodermal ridge (AER) induction. They will generate trans-species recombinant limbs to determine if the lack of AER formation is attributable to defective lgl mesenchyme or ectoderm. Differential display will be used to identify genes misexpressed in lgl which mediate the AER induction process. We also propose to use direct selection to identify additional genes from the deleted region which are expressed in the limb and may be the source of the disruption in this signaling cascade.
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