Mechanisms of Notch signaling: a simple logic deployed in time and space

Henrique, Domingos; Schweisguth, François

doi:10.1242/dev.172148

Cited by 162 publications

(109 citation statements)

References 104 publications

(142 reference statements)

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“…An animation of the basic features of the pathway is shown in Video S1, Supporting Information. However, we will not discuss the Notch signaling mechanism in any great detail, as there are numerous reviews on the subject for interested readers (Artavanis-Tsakonas & Muskavitch, 2010;Bray, 2016;Henrique & Schweisguth, 2019;Kopan & Ilagan, 2009). Hence, we will only very briefly mention some elements of the pathway that are important for our discussion in the current context.…”

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confidence: 99%

The Notch pathway in CNS homeostasis and neurodegeneration

Artavanis‐Tsakonas

Louvi

2019

WIREs Developmental Biology

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The role of the Notch signaling pathway in neural development has been well established over many years. More recent studies, however, have demonstrated that Notch continues to be expressed and active throughout adulthood in many areas of the central nervous system. Notch signals have been implicated in adult neurogenesis, memory formation, and synaptic plasticity in the adult organism, as well as linked to acute brain trauma and chronic neurodegenerative conditions. NOTCH3 mutations are responsible for the most common form of hereditary stroke, the progressive disorder cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Notch has also been associated with several progressive neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Although numerous studies link Notch activity with CNS homeostasis and neurodegenerative diseases, the data thus far are primarily correlative, rather than functional. Nevertheless, the evidence for Notch pathway activity in specific neural cellular contexts is strong, and certainly intriguing, and points to the possibility that the pathway carries therapeutic promise. This article is categorized under: Nervous System Development > Flies Signaling Pathways > Cell Fate Signaling Nervous System Development > Vertebrates: General Principles

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confidence: 99%

The Notch pathway in CNS homeostasis and neurodegeneration

Artavanis‐Tsakonas

Louvi

2019

WIREs Developmental Biology

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“…The involvement of Notch signaling in controlling cell proliferation, cell differentiation, and patterning has been studied in a vast set of contexts ranging from neuronal development to intestinal homeostasis in flies and vertebrates (Andersson et al, 2011;Bray, 2016;Henrique and Schweisguth, 2019). Spatial and temporal control of Notch activity, along with the employment of cell/tissue specific downstream elements and crosstalk with other signaling pathways, confers the functional versatility and specific reiterative use of Notch pathway activation (Andersson et al, 2011;Bray, 2016;Doroquez and Rebay, 2006;Guruharsha et al, 2012;Henrique and Schweisguth, 2019). In the Drosophila eye alone, for instance, Notch signaling has a defined and specific function at nearly every stage of tissue development and patterning (Doroquez and Rebay, 2006).…”

Section: Discussionmentioning

confidence: 99%

Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

Koca

Housden

Gault

et al. 2019

Preprint

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In all metazoans, a small number of evolutionarily conserved signaling pathways are reiteratively used during development to orchestrate critical patterning and morphogenetic processes. Among these, Notch (N) signaling is essential for most aspects of tissue patterning where it mediates the communication between adjacent cells to control cell fate specification. In Drosophila, Notch signaling is required for several features of eye development, including the R3/R4 cell fate choice and R7 specification. Here we show that hypomorphic alleles of Notchbelonging to the N facet class -reveal a novel phenotype: while photoreceptor specification in the mutant ommatidia is largely normal, defects are observed in ommatidial rotation (OR), a planar cell polarity (PCP)-mediated morphogenetic cell motility process. We demonstrate that during OR Notch signaling is specifically required in the R4 photoreceptor to upregulate the transcription of argos (aos), an inhibitory ligand to the EGFR, to fine-tune the activity of Egfr signaling. Consistently, the loss-of-function defects of N facet alleles and EGFR-signaling pathway mutants are largely indistinguishable. A Notch-regulated aos enhancer confers R4 specific expression arguing that aos is directly regulated by Notch signaling in this context via Su(H)-Mam dependent transcription. IntroductionDrosophila eye development serves as a paradigm for many developmental patterning processes and the dissection of the associated signaling pathways (Cagan and Ready, 1989a;Roignant and Treisman, 2009;Tomlinson and Ready, 1987;Wolff and Ready, 1991). The Drosophila eye consists of ~800 highly regularly arranged ommatidia, or facets, with each consisting of 8 photoreceptor (R-cell) neurons (R1-R8), arranged into a precise invariant trapezoidal pattern, and 12 accessory (cone, pigment, and bristle) cells (Tomlinson and Ready, 1987;Wolff and Ready, 1991). During larval stages, the eye develops from an imaginal disc, which is initially composed of identical pluripotent precursor cells. As a wave of cell proliferation and differentiation (referred to as morphogenetic furrow, MF) moves across the disc from posterior to anterior, it leaves regularly spaced preclusters of differentiating cells in its wake that will mature into ommatidia (Cagan and Ready, 1989a;Roignant and Treisman, 2009;Tomlinson and Ready, 1987;Wolff and Ready, 1991). At the 5-cell precluster stage, several patterning steps are apparent in addition to R-cell induction and differentiation, one being the differential specification of the two cells within the R3/R4 pair, which breaks the initial symmetry of the precluster. This differential R3/R4 specification requires the Wnt-Frizzled (Fz)/Planar Cell Polarity (PCP) pathway and its interplay with and asymmetric upregulation of Notch (N)signaling (Blair, 1999;Cooper and Bray, 1999;Fanto and Mlodzik, 1999;Mlodzik, 1999;Strutt and Strutt, 1999). This cell fate induction step is followed by the rotation of the ommatidial precluster, referred to as ommatidial rotation, towards the dors...

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“…The Notch pathway enables direct communication between neighboring cells and controls numerous cell fate decisions (Bray, 2016;Henrique and Schweisguth, 2019). Within the mammalian pathway, four Notch receptors interact in a promiscuous fashion with a set of Notch ligands, including delta like 1 (Dll1) and delta like 4 (Dll4).…”

Section: Discriminating Notch Ligandsmentioning

confidence: 99%

Communication codes in developmental signaling pathways

Elowitz

2019

Development

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A handful of core intercellular signaling pathways play pivotal roles in a broad variety of developmental processes. It has remained puzzling how so few pathways can provide the precision and specificity of cell-cell communication required for multicellular development. Solving this requires us to quantitatively understand how developmentally relevant signaling information is actively sensed, transformed and spatially distributed by signaling pathways. Recently, single cell analysis and cell-based reconstitution, among other approaches, have begun to reveal the 'communication codes' through which information is represented in the identities, concentrations, combinations and dynamics of extracellular ligands. They have also revealed how signaling pathways decipher these features and control the spatial distribution of signaling in multicellular contexts. Here, we review recent work reporting the discovery and analysis of communication codes and discuss their implications for diverse developmental processes.

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Mechanisms of Notch signaling: a simple logic deployed in time and space

Cited by 162 publications

References 104 publications

The Notch pathway in CNS homeostasis and neurodegeneration

The Notch pathway in CNS homeostasis and neurodegeneration

Notch signaling coordinates ommatidial rotation in the Drosophila eye via transcriptional regulation of the EGF-Receptor ligand Argos

Communication codes in developmental signaling pathways

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