A screen for targets of the Xenopus T-box gene Xbra

Brachyury (T), a member of the T-box gene family, is essential for the form ation of posterior mesoderm and notochord in vertebrate development. Expres sion of the Xenopus homologue of Brachyury, Xbra, causes ectopic ventral an d lateral mesoderm formation in animal cap explants and co-expression of Xb ra with Pintallavis, a forkhead/HNF3 beta-related transcription factor, ind uces notochord. Although eFGF and the Bix genes are thought to be direct ta rgets of Xbra, no other target genes have been identified. Here, we describ e the use of hormone-inducible versions of Xbra and Pintallavis to construc t cDNA libraries enriched for targets of these transcription factors. Five putative targets were isolated: Xwnt11, the homeobox gene Bix1, the zinc-fi nger transcription factor Xegr-1, a putative homologue of the antiprolifera tive gene BTG1 called Xbtg1, and BIG3/1A11, a gene of unknown function. Exp ression of Xegr-1 and Xbtg1 is controlled by Pintallavis alone as well as b y a combination of Xbra and Pintallavis. Overexpression of Xbtg1 perturbed gastrulation and caused defects in posterior tissues and in notochord and m uscle formation, a phenotype reminiscent of that observed with a dominant-n egative version of Pintallavis called Pintallavis-En(R). The Brachyury-indu cible genes we have isolated shed light on the mechanism of Brachyury funct ion during mesoderm formation. Specification of mesodermal cells is regulat ed by targets including Bix1-4 and eFGF, while gastrulation movements and p erhaps cell division are regulated by Xwnt11 and Xbtg1. (C) 2000 Elsevier S cience Ireland Ltd. All rights reserved.