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.
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Acknowledgements
We are grateful to J. C. I. Belmonte and J. F. Fallon for reading the manuscript and giving useful comments; to H. Yamamoto, K. Tsuchiya, M. Sakaizumi, N. Miyashita, H. Suzuki, A. Watanabe, H. Tamate, M. Taira, Y. Kikkawa for their gifts of valuable materials for phylogenetic analysis; to S. Brown for the gift of YAC clone I116C10; and to P. Beachy for providing Shh knockout mice, A. McMahon for the Shh probe, G. Martin for the Fgf4 probe, C. C. Hui for the Gli3 probe, and M. Scott for the Ptc probe. We thank S. Makino, S. Tanaka, A. Oka, A. Mita, K. Ishihara, S. Sakamoto, N. Saito, and K. Sorimachi for their valuable advice. This study was supported in part by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. This paper is contribution No. 2489 from the National Institute of Genetics, Japan.
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Sagai, T., Masuya, H., Tamura, M. et al. Phylogenetic conservation of a limb-specific, cis-acting regulator of Sonic hedgehog (Shh) . Mamm Genome 15, 23–34 (2004). https://doi.org/10.1007/s00335-033-2317-5
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DOI: https://doi.org/10.1007/s00335-033-2317-5