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First published online 2 September 2008
doi: 10.1242/jcs.035014

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Hairless induces cell death by downregulation of EGFR signalling activity

University of Hohenheim, Institute of Genetics (240), 70599 Stuttgart, Germany

^* Author for correspondence (e-mail: anjnagel{at}uni-hohenheim.de)

Accepted 7 July 2008

Overexpression of the Notch antagonist Hairless (H) during imaginal development in Drosophila is correlated with tissue loss and cell death. Together with the co-repressors Groucho (Gro) and C-terminal binding protein (CtBP), H assembles a repression complex on Notch target genes, thereby downregulating Notch signalling activity. Here we investigated the mechanisms underlying H-mediated cell death in S2 cell culture and in vivo during imaginal development in Drosophila. First, we mapped the domains within the H protein that are required for apoptosis induction in cell culture. These include the binding sites for the co-repressors, both of which are essential for H-mediated cell death during fly development. Hence, the underlying cause of H-mediated apoptosis seems to be a transcriptional downregulation of Notch target genes involved in cell survival. In a search for potential targets, we observed transcriptional downregulation of rho-lacZ and EGFR signalling output. Moreover, the EGFR antagonists lozenge, klumpfuss and argos were all activated upon H overexpression. This result conforms to the proapoptotic activity of H, as these factors are known to be involved in apoptosis induction. Together, the results indicate that H induces apoptosis by downregulation of EGFR signalling activity. This highlights the importance of a coordinated interplay of Notch and EGFR signalling pathways for cell survival during Drosophila development.

Key words: Argos, Apoptosis induction, EGFR signalling pathway, Hairless, Klumpfuss, Lozenge, Notch signalling pathway

This article has been cited by other articles:

				C. E. Protzer, I. Wech, and A. C. Nagel Hairless induces cell death by downregulation of EGFR signalling activity Development, October 15, 2008; 135(20): e1 - e1. [Full Text]