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Presenting Author(s) Tomoko Sagai
Abstract Title Phylogenic conservation of an intronic sequence of the Lmbr1 gene as limb specific cis-acting regulator of Shh.
Full author List Tomoko Sagai, Hiroshi Masuya, Yoichi Mizushina, Shigeharu Wakana, Masaru Tamura, Toshihiko Shiroishi
Text of abstract Polarized expression of Shh in the posterior mesenchyme of limb buds is common throughout tetrapod lineage. Ectopic expression of Shh in the anterior limb margin is correlated with the several preaxial polydactyly mutations in mouse and human. In one of the mouse mutations, Hx, a single base substitution was identified in an evolutionary conserved sequence in intron 5 of the Lmbr1 gene, residing ~800kb away from the Shh coding region (Lettice et al. 2003; Sagai et al. 2004). We reported that the conserved sequence controls polarized expression of Shh as a cis-acting regulator by cis-trans test using Shh KO allele (Sagai et al. 2004). In addition, phylogenic analysis demonstrated that the intronic sequence has been highly conserved throughout the tetrapod lineage, but not in limbless species of reptile and amphibian. Our studies and others suggest that the cis-acting regulator has been preserved through a long evolutionary period of time under constraint of limb pattern formation. Considering the long distance between the coding of Shh and the conserved sequence, higher order chromosomal structure may be involved in the cis-regulation. Our preliminary result from a gel mobility shift assay revealed that some nuclear proteins bind to the short fragment of the conserved sequence, and that the Hx mutation-type single base substitution in the fragment may change the binding specificity of the proteins.
Which session is your work most relevant to: Limb evolution