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Development, Vol 126, Issue 7 1467-1482, Copyright © 1999 by Company of Biologists
JOURNAL ARTICLES |
BI Sun, SM Bush, LA Collins-Racie, ER LaVallie, EA DiBlasio-Smith, NM Wolfman, JM McCoy and HL Sive
Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge MA 02142, USA.
TGF-beta signaling plays a key role in induction of the Xenopus mesoderm and endoderm. Using a yeast-based selection scheme, we isolated derriere, a novel TGF-beta family member that is closely related to Vg1 and that is required for normal mesodermal patterning, particularly in posterior regions of the embryo. Unlike Vg1, derriere is expressed zygotically, with RNA localized to the future endoderm and mesoderm by late blastula, and to the posterior mesoderm by mid-gastrula. The derriere expression pattern appears to be identical to the zygotic expression domain of VegT (Xombi, Brat, Antipodean), and can be activated by VegT as well as fibroblast growth factor (FGF). In turn, derriere activates expression of itself, VegT and eFGF, suggesting that a regulatory loop exists between these genes. derriere is a potent mesoderm and endoderm inducer, acting in a dose-dependent fashion. When misexpressed ventrally, derriere induces a secondary axis lacking a head, an effect that is due to dorsalization of the ventral marginal zone. When misexpressed dorsally, derriere suppresses head formation. derriere can also posteriorize neurectoderm, but appears to do so indirectly. Together, these data suggest that derriere expression is compatible only with posterior fates. In order to assess the in vivo function of derriere, we constructed a dominant interfering Derriere protein (Cm-Derriere), which preferentially blocks Derriere activity relative to that of other TGFbeta family members. Cm-derriere expression in embryos leads to posterior truncation, including defects in blastopore lip formation, gastrulation and neural tube closure. Normal expression of anterior and hindbrain markers is observed; however, paraxial mesodermal gene expression is ablated. This phenotype can be rescued by wild-type derriere and by VegT. Our findings indicate that derriere plays a crucial role in mesodermal patterning and development of posterior regions in Xenopus.
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