Evolutionary conservation, developmental expression, and genomic mapping of mammalian Twisted gastrulation

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, an d Xenopus share 72-98% identity at the amino acid level and retain all 24 c ysteine residues from Drosophila. In contrast to Drosophila where tsg expre ssion 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-beta family of secreted proteins. The vertebrat e orthologs of dpp, BMP-2 and -4, are crucial for gastrulation and neural i nduction, and aberrant signaling by BMPs and other TGF-beta family members results in developmental defects including holoprosencephaly (HPE). Interes tingly, human TSG maps to the HPE4 locus on Chromosome 18p11.3, and our ana lysis places the gene within 5 Mbp of TG-interacting factor (TGIF).