Reference Report

Reference
Citation	Carmena, A., Buff, E., Halfon, M.S., Gisselbrecht, S., Jimenez, F., Baylies, M.K., Michelson, A.M. (2002). Reciprocal regulatory interactions between the notch and ras signaling pathways in the Drosophila embryonic mesoderm. Dev. Biol. 244(2): 226--242. (Export to RIS)
FlyBase ID	FBrf0146966
Publication Type	Research paper
PubMed ID	11944933
PubMed Abstract	Convergent intercellular signals must be precisely integrated in order to elicit specific biological responses. During specification of muscle and cardiac progenitors from clusters of equivalent cells in the Drosophila embryonic mesoderm, the Ras/MAPK pathway--activated by both epidermal and fibroblast growth factor receptors--functions as an inductive cellular determination signal, while lateral inhibition mediated by Notch antagonizes this activity. A critical balance between these signals must be achieved to enable one cell of an equivalence group to segregate as a progenitor while its neighbors assume a nonprogenitor identity. We have investigated whether these opposing signals directly interact with each other, and we have examined how they are integrated by the responding cells to specify their unique fates. Our findings reveal that Ras and Notch do not function independently; rather, we have uncovered several modes of cross-talk between these pathways. Ras induces Notch, its ligand Delta, and the epidermal growth factor receptor antagonist, Argos. We show that Delta and Argos then synergize to nonautonomously block a positive autoregulatory feedback loop that amplifies a fate-inducing Ras signal. This feedback loop is characterized by Ras-mediated upregulation of proximal components of both the epidermal and fibroblast growth factor receptor pathways. In turn, Notch activation in nonprogenitors induces its own expression and simultaneously suppresses both Delta and Argos levels, thereby reinforcing a unidirectional inhibitory response. These reciprocal interactions combine to generate the signal thresholds that are essential for proper specification of progenitors and nonprogenitors from groups of initially equivalent cells.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Dev. Biol.
Title	Developmental Biology
Publication Year	1959-
ISBN/ISSN	0012-1606
Data from Reference
Alleles (13)
	aos^Δ7 Dl^X Egfr^DN.Scer\UAS htl^{DN.Scer\UAS.cMb} htl^{Scer\UAS.T:λ\cI-DD} N^{intra.hs.Scer\UAS} pnt^{P2.Scer\UAS.T:Hsim\VP16} Ras85D^{G13Q.Scer\UAS} Scer\GAL4^Mef2.PR Scer\GAL4^twi.PB spi^unspecified Su(H)^{Scer\UAS.T:Hsap\MYC,T:Hsim\VP16} T:λ\cI^DD
Constructs (9)
	P{GAL4-Mef2.R} P{GAL4-twi.B} P{UAS-Egfr.DN} P{UAS-hs.N.intra.1790} P{UAS-htl.DN.M} P{UAS-htl.λ\cI.M} P{UAS-pntP2^VP16} P{UAS-Ras85B.Act} P{UAS-Su(H).VP16}
Genes (19)
	aos Dl Egfr eve htl Kr l(1)sc N pnt Ras85D rl run Scer\GAL4 spi stumps Su(H) T:Hsap\MYC T:Hsim\VP16 T:λ\cI