Stra3/lefty, a retinoic acid-inducible novel member of the transforming growth factor-beta superfamily.

We report the structure, chromosomal localization and expression features of Stra3, a novel mouse gene whose expression is upregulated by retinoic acid in P19 embryonal carcinoma cells. The Stra3 cDNA sequence, which encodes a novel member of the TGF-beta superfamily, corresponds to, but extends more 3' than the recently published lefty sequence (Meno et al., 1996, Nature 381:151-155). The Stra3/lefty protein, which exhibits characteristics of secreted proteins, is synthesized as a precursor of 42 kDa and secreted after cleavage, suggesting that it may function as an intercellular signaling molecule. There are four exons in the Stra3/lefty gene and its 5' flanking region contains, among other putative regulatory elements, an unusual retinoid response element consisting of two half sites arranged as a palindrome, with an 8 base pairs spacer. We also show that Stra3/lefty is ectopically induced in the endodermal and ectodermal layers following in vivo administration of retinoic acid to gastrulating mouse embryos.