Regulation of Notch Signaling by a Novel Mechanism Involving Suppressor of Hairless Stability and Carboxyl Terminus-Truncated Notch

Abstract

Different amounts of Suppressor of Hairless (SuH)-dependent Notch (N) signaling is often used during animal development to produce two different tissues from a population of equipotent cells. During Drosophila melanogaster embryogenesis, cells with high amounts of this signaling differentiate the larval epidermis whereas cells with low amounts, or none, differentiate the central nervous system (CNS). The mechanism by which SuH-dependent N signaling is increased or decreased in these different cells is obscure. The developing epidermis is known to get enriched for the full-length N (NFull) and the developing CNS for the carboxyl terminus-truncated N (NΔCterm). Results described here indicate that this differential accumulation of N receptors is part of a mechanism that would promote SuH-dependent N signaling in the developing epidermis but suppress it in the developing CNS. This mechanism involves SuH-dependent stability of NFull, NFull-dependent accumulation of SuH, stage specific stability of SuH, and NΔCterm-dependent loss of SuH and NFull.

ACKNOWLEDGMENTS

We thank T. Lieber and S. Kidd for N materials; M. Young for his support of initial parts of the study; F. Schweisguth and V. Morel for SuH materials; A. Preiss and D. Maier for H antibody; J. Posakony for the UAS-H stock; A. Martinez-Arias for the N^60g11 FRT stock; M. Rand and S. Artavanis-Tsakonas for the SuH monoclonal antibody; the Drosophila Stock Center for the daGal4, hsGal4, and other fly stocks; L. Saez, and T. Lieber, S. Kidd, R. Cagan, N. Baker, and U. Wesley for comments on the manuscript.

This work was supported by the NIH (NINDS) grant NS43122-01 to C.S.W.