A vegetally localized T-box transcription factor in Xenopus eggs specifies mesoderm and endoderm and is essential for embryonic mesoderm formation

Abstract

Pattern formation in early embryogenesis is guided by maternal, localized determinants and by inductive interactions between cells. In Xenopus eggs, localized molecules have been identified and some, such as Vg1 and Xwnt-11, can specify cell fates by functioning as inducers or patterning agents. We have used differential screening to identify new Xenopus genes that regulate mesodermal patterning, and we have isolated a new member of the T-box family of transcription factors. This gene, named Brat, is expressed maternally and its transcripts are localized to the vegetal hemisphere of the egg. During early embryonic cleavage, Brat mRNA becomes partitioned primarily within vegetal cells that are fated to form the endoderm. Zygotic expression of Brat begins at the onset of gastrulation within the presumptive mesoderm of the marginal zone. Consistent with its zygotic expression pattern, Brat induces, in a dose-dependent manner, a full spectrum of mesodermal genes that mark tissues across the dorsal-ventral axis, from the blood through the Spemann organizer. Brat also induces endoderm, consistent with its vegetal localization, making Brat a good candidate for a maternal determinant of the endoderm. We tested whether endogenous Brat is required for mesoderm formation by expressing a dominant-negative, transcriptional repressor form of Brat in embryos. This treatment inhibited mesoderm formation and severely disrupted normal development, thereby establishing that Brat plays a critical role in embryonic mesoderm formation and body patterning.