Interplay of Notch and FGF signaling restricts cell fate and MAPK activation in the Drosophila trachea

Development ◽  
1999 ◽  
Vol 126 (20) ◽  
pp. 4455-4463 ◽  
Author(s):  
T. Ikeya ◽  
S. Hayashi
Keyword(s):  
Map Kinase ◽  
Cell Fate ◽  
Receptor Tyrosine Kinase ◽  
Tracheal System ◽  
Kinase Activation ◽  
Fusion Cell ◽  
Map Kinase Pathway ◽  
High Level ◽  
Drosophila Trachea ◽  
Kinase Pathway

The patterned branching in the Drosophila tracheal system is triggered by the FGF-like ligand Branchless that activates a receptor tyrosine kinase Breathless and the MAP kinase pathway. A single fusion cell at the tip of each fusion branch expresses the zinc-finger gene escargot, leads branch migration in a stereotypical pattern and contacts with another fusion cell to mediate fusion of the branches. A high level of MAP kinase activation is also limited to the tip of the branches. Restriction of such cell specialization events to the tip is essential for tracheal tubulogenesis. Here we show that Notch signaling plays crucial roles in the singling out process of the fusion cell. We found that Notch is activated in tracheal cells by Branchless signaling through stimulation of Δ expression at the tip of tracheal branches and that activated Notch represses the fate of the fusion cell. In addition, Notch is required to restrict activation of MAP kinase to the tip of the branches, in part through the negative regulation of Branchless expression. Notch-mediated lateral inhibition in sending and receiving cells is thus essential to restrict the inductive influence of Branchless on the tracheal tubulogenesis.

scholarly journals Spitz and Wingless, emanating from distinct borders, cooperate to establish cell fate across the Engrailed domain in the Drosophila epidermis

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4837-4845 ◽  
Author(s):  
L. O'Keefe ◽  
S.T. Dougan ◽  
L. Gabay ◽  
E. Raz ◽  
B.Z. Shilo ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cell Fate ◽  
Egf Receptor ◽  
Cell Types ◽  
Cell Type ◽  
Gene Encoding ◽  
Relative Level ◽  
Ets Domain ◽  
Map Kinase Pathway ◽  
Kinase Pathway

A key step in development is the establishment of cell type diversity across a cellular field. Segmental patterning within the Drosophila embryonic epidermis is one paradigm for this process. At each parasegment boundary, cells expressing the Wnt family member Wingless confront cells expressing the homeoprotein Engrailed. The Engrailed-expressing cells normally differentiate as one of two alternative cell types. In investigating the generation of this cell type diversity among the 2-cell-wide Engrailed stripe, we previously showed that Wingless, expressed just anterior to the Engrailed cells, is essential for the specification of anterior Engrailed cell fate. In a screen for additional mutations affecting Engrailed cell fate, we identified anterior open/yan, a gene encoding an inhibitory ETS-domain transcription factor that is negatively regulated by the Rasl-MAP kinase signaling cascade. We find that Anterior Open must be inactivated for posterior Engrailed cells to adopt their correct fate. This is achieved by the EGF receptor (DER), which is required autonomously in the Engrailed cells to trigger the Ras1-MAP kinase pathway. Localized activation of DER is accomplished by restricted processing of the activating ligand, Spitz. Processing is confined to the cell row posterior to the Engrailed domain by the restricted expression of Rhomboid. These cells also express the inhibitory ligand Argos, which attenuates the activation of DER in cell rows more distant from the ligand source. Thus, distinct signals flank each border of the Engrailed domain, as Wingless is produced anteriorly and Spitz posteriorly. Since we also show that En cells have the capacity to respond to either Wingless or Spitz, these cells must choose their fate depending on the relative level of activation of the two pathways.

577: The RAF/MAP Kinase Pathway Influences Survival in Androgen-Insensitive Prostate Cancer

2005 ◽  
Vol 173 (4S) ◽  
pp. 157-158
Author(s):  
Rono Mukherjee ◽  
Sarath K. Nalagatla ◽  
Mark A. Undenvood ◽  
John M.S. Bartlett ◽  
Joanne Edwards
Keyword(s):  
Prostate Cancer ◽  
Map Kinase ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals Development of anticancer drugs targeting the MAP kinase pathway

Oncogene ◽  
2000 ◽  
Vol 19 (56) ◽  
pp. 6594-6599 ◽  
Author(s):  
Judith S Sebolt-Leopold
Keyword(s):  
Map Kinase ◽  
Anticancer Drugs ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals The MADD-3 LAMMER Kinase Interacts with a p38 MAP Kinase Pathway to Regulate the Display of the EVA-1 Guidance Receptor in Caenorhabditis elegans

PLoS Genetics ◽  
2016 ◽  
Vol 12 (4) ◽  
pp. e1006010 ◽  
Author(s):  
Serena A. D’Souza ◽  
Luckshi Rajendran ◽  
Rachel Bagg ◽  
Louis Barbier ◽  
Derek M. van Pel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Caenorhabditis Elegans ◽  
Map Kinase ◽  
Motor Neurons ◽  
Leading Edge ◽  
P38 Map Kinase ◽  
Endosomal Trafficking ◽  
Guidance Cue ◽  
Map Kinase Pathway ◽  
Kinase Pathway

The proper display of transmembrane receptors on the leading edge of migrating cells and cell extensions is essential for their response to guidance cues. We previously discovered that MADD-4, which is an ADAMTSL secreted by motor neurons in Caenorhabditis elegans, interacts with an UNC-40/EVA-1 co-receptor complex on muscles to attract plasma membrane extensions called muscle arms. In nematodes, the muscle arm termini harbor the post-synaptic elements of the neuromuscular junction. Through a forward genetic screen for mutants with disrupted muscle arm extension, we discovered that a LAMMER kinase, which we call MADD-3, is required for the proper display of the EVA-1 receptor on the muscle’s plasma membrane. Without MADD-3, EVA-1 levels decrease concomitantly with a reduction of the late-endosomal marker RAB-7. Through a genetic suppressor screen, we found that the levels of EVA-1 and RAB-7 can be restored in madd-3 mutants by eliminating the function of a p38 MAP kinase pathway. We also found that EVA-1 and RAB-7 will accumulate in madd-3 mutants upon disrupting CUP-5, which is a mucolipin ortholog required for proper lysosome function. Together, our data suggests that the MADD-3 LAMMER kinase antagonizes the p38-mediated endosomal trafficking of EVA-1 to the lysosome. In this way, MADD-3 ensures that sufficient levels of EVA-1 are present to guide muscle arm extension towards the source of the MADD-4 guidance cue.

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