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Presenting Author(s) Masaki Hosoya
Abstract Title Genetic dissection of the network of limb A-P axis formation with preaxial polydactylous mouse mutants.
Full author List Masaki HOSOYA, Yukari YADA, Tomoko SAGAI, Hiroshi MASUYA, Shigeru MAKINO, Toshihiko SHIROISHI
Text of abstract Numerous mouse mutants show preaxial polydactyly. Causative genes for the most of them have not yet been identified, suggesting presence of many novel genes involved in the limb A-P axis formation. For genetic dissection of the network that controls limb development, we have done fine characterization of the phenotypes of three such mutants, luxate (lx), X-linked polydactyly (Xpl), and Recombination induced mutation-4 (Rim4), all of which are affected the A-P axis formation. We first examined expression patterns of marker genes known to be involved in the A-P axis formation of limbs. The Xpl embryos showed ectopic Shh expression in the anterior margin of the hindlimb buds, but no ectopic expression of the other genes before the ectopic Shh expression. In lx and Rim4, the Shh expression domain in the posterior side of the limb buds was shifted anteriorly as compared with wild-type embryos, suggesting that the limb A-P axis formation is disrupted from the initial stage of limb development. The expression of dHAND, Gli3 and Alx4 was normal in Rim4 embryos, but shifted anteriorly in the lx limb buds. The result indicated that Rim4 causative gene acts in the downstream of the dHAND, Gli3 and Alx4 genes, while lx in the upstream of the above genes, and is independent of Shh. We generated mutant mice homozygous for both Shh-null and lx alleles to clarify whether the lx causative gene is involved in the Shh-independent cascade including Gli3. The double mutants exhibited phenotype very similar to single Shh-null mutants. In conclusion, Xpl acts in the downstream of the Shh signaling and mediates the Shh-dependent signaling during limb morphogenesis. lx is likely involved in both Shh-independent early stage of limb development and Shh-dependent later stage. Rim4 likely controls the position of Shh induction in the posterior margin of limb buds.
Which session is your work most relevant to: Limb patterning