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Dynamic Ligand Discrimination in the Notch Signaling Pathway.

Cell | 2018

The Notch signaling pathway comprises multiple ligands that are used in distinct biological contexts. In principle, different ligands could activate distinct target programs in signal-receiving cells, but it is unclear how such ligand discrimination could occur. Here, we show that cells use dynamics to discriminate signaling by the ligands Dll1 and Dll4 through the Notch1 receptor. Quantitative single-cell imaging revealed that Dll1 activates Notch1 in discrete, frequency-modulated pulses that specifically upregulate the Notch target gene Hes1. By contrast, Dll4 activates Notch1 in a sustained, amplitude-modulated manner that predominantly upregulates Hey1 and HeyL. Ectopic expression of Dll1 or Dll4 in chick neural crest produced opposite effects on myogenic differentiation, showing that ligand discrimination can occur in vivo. Finally, analysis of chimeric ligands suggests that ligand-receptor clustering underlies dynamic encoding of ligand identity. The ability of the pathway to utilize ligands as distinct communication channels has implications for diverse Notch-dependent processes.

Pubmed ID: 29398116 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


ChIP-seq (tool)

RRID:SCR_001237

Set of software modules for performing common ChIP-seq data analysis tasks across the whole genome, including positional correlation analysis, peak detection, and genome partitioning into signal-rich and signal-poor regions. The tools are designed to be simple, fast and highly modular. Each program carries out a well defined data processing procedure that can potentially fit into a pipeline framework. ChIP-Seq is also freely available on a Web interface.

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Imaris (tool)

RRID:SCR_007370

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TopHat (tool)

RRID:SCR_013035

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RRID:SCR_014597

Software tool for transcriptome assembly and differential expression analysis for RNA-Seq. Includes script called cuffmerge that can be used to merge together several Cufflinks assemblies. It also handles running Cuffcompare as well as automatically filtering a number of transfrags that are likely to be artifacts. If the researcher has a reference GTF file, the researcher can provide it to the script to more effectively merge novel isoforms and maximize overall assembly quality.

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RRID:SCR_007303

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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RRID:SCR_003070

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MATLAB (software resource)

RRID:SCR_001622

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C2C12 (cell line)

RRID:CVCL_0188

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T-REx-CHO (cell line)

RRID:CVCL_D586

Cell line T-REx-CHO is a Spontaneously immortalized cell line with a species of origin Cricetulus griseus (Chinese hamster)

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CHO-K1 (cell line)

RRID:CVCL_0214

Cell line CHO-K1 is a Spontaneously immortalized cell line with a species of origin Cricetulus griseus (Chinese hamster)

View all literature mentions

CHO-K1 (cell line)

RRID:CVCL_0214

Cell line CHO-K1 is a Spontaneously immortalized cell line with a species of origin Cricetulus griseus (Chinese hamster)

View all literature mentions

C2C12 (cell line)

RRID:CVCL_0188

Cell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)

View all literature mentions

T-REx-CHO (cell line)

RRID:CVCL_D586

Cell line T-REx-CHO is a Spontaneously immortalized cell line with a species of origin Cricetulus griseus (Chinese hamster)

View all literature mentions

C2C12 (cell line)

RRID:CVCL_0188

Cell line C2C12 is a Spontaneously immortalized cell line with a species of origin Mus musculus (Mouse)

View all literature mentions