Antagonistic growth regulation by Dpp and Fat drives uniform cell proliferation.
We use the Dpp morphogen gradient in the Drosophila wing disc as a model to address the fundamental question of how a gradient of a growth factor can produce uniform growth. We first show that proper expression and subcellular localization of components in the Fat tumor-suppressor pathway, which have been argued to depend on Dpp activity differences, are not reliant on the Dpp gradient. We next analyzed cell proliferation in discs with uniformly high Dpp or uniformly low Fat signaling activity and found that these pathways regulate growth in a complementary manner. While the Dpp mediator Brinker inhibits growth in the primordium primarily in the lateral regions, Fat represses growth mostly in the medial region. Together, our results indicate that the activities of both signaling pathways are regulated in a parallel rather than sequential manner and that uniform proliferation is achieved by their complementary action on growth.
Institute of Molecular Life Sciences, Winterthurerstr. 190, 8057 Zurich, Switzerland.
Gerald
G
Schwank
Gerardo
G
Tauriello
Ryohei
R
Yagi
Elizabeth
E
Kranz
Petros
P
Koumoutsakos
Konrad
K
Basler
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D016764:Cell Polarity; D049109:Cell Proliferation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000254:growth & development*; D018507:Gene Expression Regulation, Developmental; D008954:Models, Biological; D015398:Signal Transduction; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology / Q000378:metabolism
D015815:Cell Adhesion Molecules; D029721:Drosophila Proteins; C064196:dpp protein, Drosophila; C472307:ft protein, Drosophila