D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis.
During Drosophila oogenesis, asymmetrically localized Gurken activates the EGF receptor (Egfr) and determines dorsal follicle cell fates. Using a mosaic follicle cell system we have identified a mutation in the D-cbl gene which causes hyperactivation of the Egfr pathway. Cbl proteins are known to downregulate activated receptors. We find that the abnormal Egfr activation is ligand dependent. Our results show that the precise regulation of Egfr activity necessary to establish different follicle cell fates requires two levels of control. The localized ligand Gurken activates Egfr to different levels in different follicle cells. In addition, Egfr activity has to be repressed through the activity of D-cbl to ensure the absence of signaling in the ventral most follicle cells.
Pai
L M
LM
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, New Jersey 08544, USA.
Barcelo
G
G
Schüpbach
T
T
D000483:Alleles; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002999:Clone Cells / Q000378:metabolism; D004252:DNA Mutational Analysis; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins; D005314:Embryonic and Fetal Development / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D019476:Insect Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009866:Oogenesis / Q000235:genetics*; D006080:Ovarian Follicle / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D010063:Ovum / Q000254:growth & development; D011247:Pregnancy; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl; D015398:Signal Transduction / Q000235:genetics*; D015238:Sulfotransferases / Q000235:genetics; D016211:Transforming Growth Factor alpha; D015291:Transforming Growth Factors / Q000235:genetics
D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D016211:Transforming Growth Factor alpha; C083730:grk protein, Drosophila; D015291:Transforming Growth Factors; D050721:Proto-Oncogene Proteins c-cbl; D066246:ErbB Receptors; D015238:Sulfotransferases; C115847:pip protein, Drosophila; C105053:Kek1 protein, Drosophila; D017027:Protein Tyrosine Phosphatases; C106411:Cbl protein, Drosophila