Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 27 January 2009
Vol. 2, Issue 55, p. ra1
[DOI: 10.1126/scisignal.2000140]


Direct Response to Notch Activation: Signaling Crosstalk and Incoherent Logic

Alena Krejcí*, Fred Bernard*, Ben E. Housden*, Stephanie Collins, and Sarah J. Bray{dagger}

Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

* These authors contributed equally to this work.

Abstract: Notch is the receptor in one of a small group of conserved signaling pathways that are essential at multiple stages in development. Although the mechanism of transduction impinges directly on the nucleus to regulate transcription through the CSL [CBF-1/Su(H)/LAG-1] DNA binding protein, there are few known direct target genes. Thus, relatively little is known about the immediate cellular consequences of Notch activation. We therefore set out to determine the genome-wide response to Notch activation by analyzing the changes in messenger RNA (mRNA) expression and the sites of CSL occupancy within 30 minutes of activating Notch in Drosophila cells. Through combining these data, we identify high-confidence direct targets of Notch that are implicated in the maintenance of adult muscle progenitors in vivo. These targets are enriched in cell morphogenesis genes and in components of other cell signaling pathways, especially the epidermal growth factor receptor (EGFR) pathway. Also evident are examples of incoherent network logic, where Notch stimulates the expression of both a gene and the repressor of that gene, which may result in a transient window of competence after Notch activation. Furthermore, because targets comprise both positive and negative regulators, cells become poised for both outcomes, suggesting one mechanism through which Notch activation can lead to opposite effects in different contexts.

{dagger} To whom correspondence should be addressed. E-mail: sjb32{at}

Citation: A. Krejcí, F. Bernard, B. E. Housden, S. Collins, S. J. Bray, Direct Response to Notch Activation: Signaling Crosstalk and Incoherent Logic. Sci. Signal. 2, ra1 (2009).

Read the Full Text

Dynamic CRM occupancy reflects a temporal map of developmental progression.
B. Wilczynski and E. E. M. Furlong (2014)
Mol Syst Biol 6, 383
   Abstract »    Full Text »    PDF »
Context-Dependent Enhancer Selection Confers Alternate Modes of Notch Regulation on argos.
B. E. Housden, A. Terriente-Felix, and S. J. Bray (2014)
Mol. Cell. Biol. 34, 664-672
   Abstract »    Full Text »    PDF »
Machine learning classification of cell-specific cardiac enhancers uncovers developmental subnetworks regulating progenitor cell division and cell fate specification.
S. M. Ahmad, B. W. Busser, D. Huang, E. J. Cozart, S. Michaud, X. Zhu, N. Jeffries, A. Aboukhalil, M. L. Bulyk, I. Ovcharenko, et al. (2014)
Development 141, 878-888
   Abstract »    Full Text »    PDF »
A Serrate-Notch-Canoe complex mediates essential interactions between glia and neuroepithelial cells during Drosophila optic lobe development.
R. Perez-Gomez, J. Slovakova, N. Rives-Quinto, A. Krejci, and A. Carmena (2013)
J. Cell Sci. 126, 4873-4884
   Abstract »    Full Text »    PDF »
Specific fate decisions in adult hepatic progenitor cells driven by MET and EGFR signaling.
M. Kitade, V. M. Factor, J. B. Andersen, A. Tomokuni, K. Kaji, H. Akita, A. Holczbauer, D. Seo, J. U. Marquardt, E. A. Conner, et al. (2013)
Genes & Dev. 27, 1706-1717
   Abstract »    Full Text »    PDF »
Notch cooperates with Lozenge/Runx to lock haemocytes into a differentiation programme.
A. Terriente-Felix, J. Li, S. Collins, A. Mulligan, I. Reekie, F. Bernard, A. Krejci, and S. Bray (2013)
Development 140, 926-937
   Abstract »    Full Text »    PDF »
Hes repressors are essential regulators of hematopoietic stem cell development downstream of Notch signaling.
J. Guiu, R. Shimizu, T. D'Altri, S. T. Fraser, J. Hatakeyama, E. H. Bresnick, R. Kageyama, E. Dzierzak, M. Yamamoto, L. Espinosa, et al. (2013)
J. Exp. Med. 210, 71-84
   Abstract »    Full Text »    PDF »
Dissecting the mechanisms of Notch induced hyperplasia.
A. Djiane, A. Krejci, F. Bernard, S. Fexova, K. Millen, and S. J. Bray (2013)
EMBO J. 32, 60-71
   Abstract »    Full Text »    PDF »
Bidirectional Notch activation represses fusion competence in swarming adult Drosophila myoblasts.
B. Gildor, E. D. Schejter, and B.-Z. Shilo (2012)
Development 139, 4040-4050
   Abstract »    Full Text »    PDF »
Notch signalling in smooth muscle cells during development and disease.
C. Fouillade, M. Monet-Lepretre, C. Baron-Menguy, and A. Joutel (2012)
Cardiovasc Res 95, 138-146
   Abstract »    Full Text »    PDF »
bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation.
E. Zacharioudaki, S. S. Magadi, and C. Delidakis (2012)
Development 139, 1258-1269
   Abstract »    Full Text »    PDF »
The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development.
B. W. Heck, B. Zhang, X. Tong, Z. Pan, W.-M. Deng, and C.-C. Tsai (2012)
Biology Open 1, 182-196
   Abstract »    Full Text »    PDF »
CoREST acts as a positive regulator of Notch signaling in the follicle cells of Drosophila melanogaster.
E. Domanitskaya and T. Schupbach (2012)
J. Cell Sci. 125, 399-410
   Abstract »    Full Text »    PDF »
The transcriptional corepressor SMRTER influences both Notch and ecdysone signaling during Drosophila development.
B. W. Heck, B. Zhang, X. Tong, Z. Pan, W.-M. Deng, and C.-C. Tsai (2012)
Biology Open
   Abstract »    Full Text »    PDF »
Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila.
Y. Song and B. Lu (2011)
Genes & Dev. 25, 2644-2658
   Abstract »    Full Text »    PDF »
Notch signaling: simplicity in design, versatility in function.
E. R. Andersson, R. Sandberg, and U. Lendahl (2011)
Development 138, 3593-3612
   Abstract »    Full Text »    PDF »
The Drosophila STUbL protein Degringolade limits HES functions during embryogenesis.
K. C. Barry, M. Abed, D. Kenyagin, T. R. Werwie, O. Boico, A. Orian, and S. M. Parkhurst (2011)
Development 138, 1759-1769
   Abstract »    Full Text »    PDF »
Targeting Notch signalling by the conserved miR-8/200 microRNA family in development and cancer cells.
D. M. Vallejo, E. Caparros, and M. Dominguez (2011)
EMBO J. 30, 756-769
   Abstract »    Full Text »    PDF »
Specificity of Notch pathway activation: Twist controls the transcriptional output in adult muscle progenitors.
F. Bernard, A. Krejci, B. Housden, B. Adryan, and S. J. Bray (2010)
Development 137, 2633-2642
   Abstract »    Full Text »    PDF »
Reprogramming of T Cells to Natural Killer-Like Cells upon Bcl11b Deletion.
P. Li, S. Burke, J. Wang, X. Chen, M. Ortiz, S.-C. Lee, D. Lu, L. Campos, D. Goulding, B. L. Ng, et al. (2010)
Science 329, 85-89
   Abstract »    Full Text »    PDF »
Drosophila adult muscle precursors form a network of interconnected cells and are specified by the rhomboid-triggered EGF pathway.
N. Figeac, T. Jagla, R. Aradhya, J. P. Da Ponte, and K. Jagla (2010)
Development 137, 1965-1973
   Abstract »    Full Text »    PDF »
The H3K27me3 Demethylase dUTX Is a Suppressor of Notch- and Rb-Dependent Tumors in Drosophila.
H. M. Herz, L. D. Madden, Z. Chen, C. Bolduc, E. Buff, R. Gupta, R. Davuluri, A. Shilatifard, I. K. Hariharan, and A. Bergmann (2010)
Mol. Cell. Biol. 30, 2485-2497
   Abstract »    Full Text »    PDF »
The cytolinker Pigs is a direct target and a negative regulator of Notch signalling.
M. K. Pines, B. E. Housden, F. Bernard, S. J. Bray, and K. Roper (2010)
Development 137, 913-922
   Abstract »    Full Text »    PDF »
Drosophila Hey is a target of Notch in asymmetric divisions during embryonic and larval neurogenesis.
M. Monastirioti, N. Giagtzoglou, K. A. Koumbanakis, E. Zacharioudaki, M. Deligiannaki, I. Wech, M. Almeida, A. Preiss, S. Bray, and C. Delidakis (2010)
Development 137, 191-201
   Abstract »    Full Text »    PDF »
Nodal points and complexity of Notch-Ras signal integration.
G. D. Hurlbut, M. W. Kankel, and S. Artavanis-Tsakonas (2009)
PNAS 106, 2218-2223
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882