Phylogenetic conservation of a limb-specific, <Emphasis Type="Italic">cis</Emphasis>-acting regulator of Sonic hedgehog (<Emphasis Type="Italic">Shh</Emphasis>) |
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Authors: | Tomoko?Sagai Hiroshi?Masuya Masaru?Tamura Kunihiko?Shimizu Yukari?Yada Shigeharu?Wakana Yoichi?Gondo Tetsuo?Noda Email author" target="_blank">Toshihiko?ShiroishiEmail author |
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Institution: | (1) Mammalian Genetics Laboratory, National Institute of Genetics, Yata-1111, Mishima, Shizuoka-ken 411-8540, Japan;(2) Mouse Functional Genomics Research Group, Riken Genomic Sciences Center, 214 Maeda-cho, Totsuka-ku, Yokohama, Kanagawa 244-0804, Japan;(3) Department of Pedodontics, Nihon University Graduate School of Dentistry at Matudo, 2-870-1 Sakaecho-Nishi, Matudo, Chiba, 271, Japan;(4) Population and Quantitative Genomics Team, Bioinformatics Group, Riken Genomic Sciences Center, 214 Maeda-cho, Totsuka-ku, Yokohama, Kanagawa 244-0804, Japan |
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Abstract: | Polarized expression of the Sonic hedgehog (Shh) gene in the posterior mesenchyme is essential for pattern formation in the appendages of higher vertebrates, from teleost fins to tetrapod limb buds. We report on a sequence in intron 5 of the Lmbr1 gene, which resides approximately 1 Mb from the Shh coding region in the mouse genome and is highly conserved among teleost fishes and throughout the tetrapod lineage. Positional cloning revealed that two mouse mutations, Hx and M100081, characterized by mirror-image digit duplication and ectopic anterior Shh expression, have base substitutions in this sequence. Absence of the conserved sequence in limbless reptiles and amphibians and a cis-trans test using the Hx and Shh KO alleles suggest that the sequence is a cis-acting regulator that controls the polarized expression of Shh.
The nucleotide sequence data reported in this paper have been submitted to GenBank and have been assigned the accession number: AB092986 to AB093004, AB093207, and AB114903. |
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