Evolutionary conservation, developmental expression, and genomic mapping of mammalian Twisted gastrulation |
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| Authors: | Daniel Graf Paula M Timmons Megan Hitchins Vasso Episkopou Gudrun Moore Takekito Ito Asao Fujiyama Amanda G Fisher Matthias Merkenschlager |
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| Institution: | (1) Lymphocyte Development Group, MRC Clinical Sciences Centre, Du Cane Road, London W12 0NN, UK, GB;(2) Mammalian Neurogenesis Group, MRC Clinical Sciences Centre, Du Cane Road, London W12 0NN, UK, GB;(3) Department of Fetal and Maternal Medicine, IRDB Imperial College School of Medicine, London, UK, GB;(4) RIKEN Genomic Sciences Center, Kanagawa, Japan, JP;(5) Mitsubishi Research Institute, Tokyo, Japan, JP |
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| Abstract: | The twisted gastrulation gene (tsg) encodes a secreted protein required for the correct specification of dorsal midline cell fate during gastrulation in Drosophila. We report that tsg homologs from human, mouse, zebrafish, and Xenopus share 72–98% identity at the amino acid level and retain all 24 cysteine residues from Drosophila. In contrast to Drosophila where tsg expression is limited to early embryos, expression is found throughout mouse and human development. In Drosophila, tsg acts in synergy with decapentaplegic (dpp), a member of the TGF-β family of secreted proteins. The vertebrate orthologs of dpp, BMP-2 and -4, are crucial for gastrulation and neural induction, and aberrant signaling by BMPs and other TGF-β family members
results in developmental defects including holoprosencephaly (HPE). Interestingly, human TSG maps to the HPE4 locus on Chromosome
18p11.3, and our analysis places the gene within 5 Mbp of TG-interacting factor (TGIF).
Received: 21 August 2000 / Accepted: 9 March 2001 |
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