An activity of Notch regulates JNK signalling and affects dorsal closure in Drosophila

Background: The Drosophila Notch protein is a receptor that controls cell f ate during embryonic development, particularly in lateral inhibition, a pro cess that acts on groups of cells that share a particular developmental pot ential to restrict the number of cells that will adopt that cell fate. The process of lateral inhibition is implemented by the nuclear protein Suppres sor of Hairless (Su(H)) and is triggered by the ligand Delta. Recent result s have shown that the interaction between Delta and Notch triggers the clea vage of the intracellular domain of Notch which then translocates to the nu cleus and binds to Su(H). Results: We find that Notch plays a role in the patterning of the dorsal ep idermis of the Drosophila embryo and that this function of Notch is indepen dent of Su(H), requires Notch at the plasma membrane and targets the c-Jun N-terminal kinase (JNK) signalling pathway. Notch mutants show high levels of JNK activity and can rescue the effects of lowered JNK signalling result ing from mutations in the hemipterous and basket genes. Two regions of the intracellular domain of Notch are involved: the Cdc10/ankyrin repeats, whic h downregulate signalling through the JNK pathway, and a region carboxy-ter minal to these repeats, which regulates this negative function. Conclusions: Our results reveal a novel signalling activity of Notch that d oes not require its cleavage and acts by modulating signalling through the JNK pathway. In the Drosophila embryo, this activity plays an important rol e in the morphogenetic movements that drive dorsal closure.