Decoding the Notch signal

Falo‐Sanjuan, Julia; Bray, Sarah

doi:10.1111/dgd.12644

Cited by 54 publications

(47 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To account for possible differences in fluorescence levels between movies, mean intensity values were normalised to an average of the whole movie. The tracking and posterior analysis codes were implemented in MATLAB (2018a, Mathworks) and R respectively and the scripts are available at https://github.com/juliafs93/CellTracker (Falo Sanjuan, 2019; copy archived at https://github.com/elifesciences-publications/CellTracker).…”

Section: Methodsmentioning

confidence: 99%

Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling

Zacharioudaki

Falo‐Sanjuan

Bray

2019

eLife

Self Cite

View full text Add to dashboard Cite

To progress towards differentiation, progeny of stem cells need to extinguish expression of stem-cell maintenance genes. Failures in such mechanisms can drive tumorigenesis. In Drosophila neural stem cell (NSC) lineages, excessive Notch signalling results in supernumerary NSCs causing hyperplasia. However, onset of hyperplasia is considerably delayed implying there are mechanisms that resist the mitogenic signal. Monitoring the live expression of a Notch target gene, E(spl)mγ, revealed that normal attenuation is still initiated in the presence of excess Notch activity so that re-emergence of NSC properties occurs only in older progeny. Screening for factors responsible, we found that depletion of Mi-2/NuRD ATP remodeling complex dramatically enhanced Notch-induced hyperplasia. Under these conditions, E(spl)mγ was no longer extinguished in NSC progeny. We propose that Mi-2 is required for decommissioning stem-cell enhancers in their progeny, enabling the switch towards more differentiated fates and rendering them insensitive to mitogenic factors such as Notch.

show abstract

Section: Methodsmentioning

confidence: 99%

Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling

Zacharioudaki

Falo‐Sanjuan

Bray

2019

eLife

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast to many signaling pathways, Notch pathway lacks intermediate steps and does not exploit downstream secondary messengers for signal amplification. Binding of a ligand to Notch receptor results in receptor cleavage and translocation of Notch intracellular domain (NICD) to the nucleus, where it interacts with a transcription factor recombination signal binding protein (RBP-J), and Mastermind-like 1 [20]. The Notch co-activator complex induces the expression of target genes belonging to hairy/enhancer of split (Hes) and Hes-related with YRPW (Tyr-Arg-Pro-Trp) motif 1 (Hey) families [21].…”

Section: Of 22mentioning

confidence: 99%

Crosstalk between Androgen-ZIP9 Signaling and Notch Pathway in Rodent Sertoli Cells

Kamińska

Marek

Pardyak

et al. 2020

IJMS

View full text Add to dashboard Cite

Our recent study demonstrated altered expression of Notch ligands, receptors, and effector genes in testes of pubertal rats following reduced androgen production or signaling. Herein we aimed to explore the role of nuclear androgen receptor (AR) and membrane androgen receptor (Zrt- and Irt-like protein 9; ZIP9) in the regulation of Notch pathway activation in rodent Sertoli cells. Experiments were performed using TM4 and 15P-1 Sertoli cell lines and rat primary Sertoli cells (PSC). We found that testosterone (10−8 M–10−6 M) increased the expression of Notch1 receptor, its active form Notch1 intracellular domain (N1ICD) (p < 0.05, p < 0.01, p < 0.001), and the effector genes Hey1 (p < 0.05, p < 0.01, p < 0.001) and Hes1 (p < 0.05, p < 0.001) in Sertoli cells. Knockdown of AR or ZIP9 as well as antiandrogen exposure experiments revealed that (i) action of androgens via both AR and ZIP9 controls Notch1/N1ICD expression and transcriptional activity of recombination signal binding protein (RBP-J), (ii) AR-dependent signaling regulates Hey1 expression, (iii) ZIP9-dependent pathway regulates Hes1 expression. Our findings indicate a crosstalk between androgen and Notch signaling in Sertoli cells and point to cooperation of classical and non-classical androgen signaling pathways in controlling Sertoli cell function.

show abstract

“…Such features may lead one to ask whether in the due course of evolution there emerged mechanisms equipping biological systems with the capacity of modulating noise to exploit it functionally [ 9 , 10 , 11 , 12 ]. One example is the ubiquitous bursty gene expression [ 13 , 14 ] taking place during Drosophila embryogenesis when the gene networks govern multiple proteins to have proper amounts within proper spatial and temporal ranges during pattern formation [ 15 , 16 , 17 ]. For such patterns to be achieved, the activation and inactivation of the promoters of the genes of developmental networks should be modulated with sufficient precision.…”

Section: Introductionmentioning

confidence: 99%

Binary Expression Enhances Reliability of Messaging in Gene Networks

Gama

Giovanini

Balázsi

et al. 2020

Entropy

View full text Add to dashboard Cite

The promoter state of a gene and its expression levels are modulated by the amounts of transcription factors interacting with its regulatory regions. Hence, one may interpret a gene network as a communicating system in which the state of the promoter of a gene (the source) is communicated by the amounts of transcription factors that it expresses (the message) to modulate the state of the promoter and expression levels of another gene (the receptor). The reliability of the gene network dynamics can be quantified by Shannon’s entropy of the message and the mutual information between the message and the promoter state. Here we consider a stochastic model for a binary gene and use its exact steady state solutions to calculate the entropy and mutual information. We show that a slow switching promoter with long and equally standing ON and OFF states maximizes the mutual information and reduces entropy. That is a binary gene expression regime generating a high variance message governed by a bimodal probability distribution with peaks of the same height. Our results indicate that Shannon’s theory can be a powerful framework for understanding how bursty gene expression conciliates with the striking spatio-temporal precision exhibited in pattern formation of developing organisms.

show abstract

Decoding the Notch signal

Cited by 54 publications

References 104 publications

Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling

Mi-2/NuRD complex protects stem cell progeny from mitogenic Notch signaling

Crosstalk between Androgen-ZIP9 Signaling and Notch Pathway in Rodent Sertoli Cells

Binary Expression Enhances Reliability of Messaging in Gene Networks

Contact Info

Product

Resources

About