Transcriptional control of Notch signaling by a HOX and a PBX/EXD protein during vulval development in C. elegans
Takács-Vellai, KrisztinaDepartment of Genetics, Eötvös Loránd University, Budapest, Hungary - Department of Biology, University of Fribourg, Switzerland
Vellai, TiborDepartment of Genetics, Eötvös Loránd University, Budapest, Hungary
Chen, Estella B.Yale University School of Medicine, Department of Genetics, New Haven, CT, USA - Department of Biological and Physical Sciences, Kennesaw State University, Kennesaw, USA
Zhang, YueDepartment of Biology, University of Fribourg, Switzerland
Guerry, FrédéricDepartment of Biology, University of Fribourg, Switzerland
Stern, Michael J.Yale University School of Medicine, Department of Genetics, New Haven, CT, USA
Müller, FritzDepartment of Biology, University of Fribourg, Switzerland
English
The Notch signaling pathway controls growth, differentiation and patterning in divergent animal phyla; in humans, defective Notch signaling has been implicated in cancer, stroke and neurodegenerative disorders. Despite its developmental and medical significance, little is known about the factors that render cells to become competent for Notch signaling. Here we show that during vulval development in the nematode Caenorhabditis elegans the HOX protein LIN-39 and its EXD/PBX-like cofactor CEH-20 are required for LIN-12/Notch-mediated lateral signaling that specifies the 2° vulval cell fate. Inactivation of either lin-39 or ceh-20 resulted in the misspecification of 2° vulval cells and suppressed the multivulva phenotype of lin-12(n137) gain-of-function mutant animals. Furthermore, both LIN-39 and CEH-20 are required for the expression of basal levels of the genes encoding the LIN-12/Notch receptor and one of its ligands in the vulval precursor cells, LAG-2/Delta/Serrate, rendering them competent for the subsequent lin-12/Notch induction events. Our results suggest that the transcription factors LIN-39 and CEH-20, which function at the bottom of the RTK/Ras and Wnt pathways in vulval induction, serve as major integration sites in coordinating and transmitting signals to the LIN-12/Notch cascade to regulate vulval cell fates.