Drosophila WntD is a target and an inhibitor of the Dorsal/Twist/Snail network in the gastrulating embryo.
The maternal Toll signaling pathway sets up a nuclear gradient of the transcription factor Dorsal in the early Drosophila embryo. Dorsal activates twist and snail, and the Dorsal/Twist/Snail network activates and represses other zygotic genes to form the correct expression patterns along the dorsoventral axis. An essential function of this patterning is to promote ventral cell invagination during mesoderm formation, but how the downstream genes regulate ventral invagination is not known. We show here that wntD is a novel member of the Wnt family. The expression of wntD is activated by Dorsal and Twist, but the expression is much reduced in the ventral cells through repression by Snail. Overexpression of WntD in the early embryo inhibits ventral invagination, suggesting that the de-repressed WntD in snail mutant embryos may contribute to inhibiting ventral invagination. The overexpressed WntD inhibits invagination by antagonizing Dorsal nuclear localization, as well as twist and snail expression. Consistent with the early expression of WntD at the poles in wild-type embryos, loss of WntD leads to posterior expansion of nuclear Dorsal and snail expression, demonstrating that physiological levels of WntD can also attenuate Dorsal nuclear localization. We also show that the de-repressed WntD in snail mutant embryos contributes to the premature loss of snail expression, probably by inhibiting Dorsal. Thus, these results together demonstrate that WntD is regulated by the Dorsal/Twist/Snail network, and is an inhibitor of Dorsal nuclear localization and function.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Atish
A
Ganguly
Jin
J
Jiang
Y Tony
YT
Ip
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005775:Gastrula / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D010750:Phosphoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D051879:Twist-Related Protein 1; D016335:Zinc Fingers
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; C504611:WntD protein, Drosophila; C062236:dl protein, Drosophila; C000604451:sna protein, Drosophila