Modeling the Notch Response

Binshtok, Udi; Sprinzak, David

doi:10.1007/978-3-319-89512-3_5

Cited by 24 publications

(25 citation statements)

References 53 publications

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“…To determine whether the pattern of neuronal differentiation can be explained by Delta-Notch-mediated lateral inhibition delivered via transient basal protrusions, we developed a physical description of lateral inhibition coupled to the observed protrusions dynamics. The dynamics of Delta-Notch signalling have been modelled extensively ( Binshtok and Sprinzak, 2018 ). Here we built on Cohen et al.…”

Section: Resultsmentioning

confidence: 99%

Basal Protrusions Mediate Spatiotemporal Patterns of Spinal Neuron Differentiation

et al. 2019

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Summary During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging in zebrafish reveals that differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord before axon initiation. These protrusions express Delta protein, consistent with the hypothesis they influence Notch signaling at a distance of several cell diameters. Experimental reduction of Laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that neuronal differentiation pattern is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers a stereotyped protrusive activity of newborn neurons that organize long-distance spatiotemporal patterning of differentiation.

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Section: Resultsmentioning

confidence: 99%

Basal Protrusions Mediate Spatiotemporal Patterns of Spinal Neuron Differentiation

et al. 2019

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“…To determine whether the pattern of neuronal differentiation can be explained by Delta Notch mediated lateral inhibition delivered via transient basal protrusions, we developed a physical description of lateral inhibition coupled to the observed protrusions dynamics. The dynamics of Delta Notch signalling have been modelled extensively (Binshtok and Sprinzak, 2018). Here we built on (Cohen et al, 2010) and (Collier et al, 1996) and describe the process of lateral inhibition by, We first performed simulations to predict the distribution of dx assuming differentiation events occur randomly along the spinal cord ( Figure 8A).…”

Section: Theoretical Predictions Support the Role Of Basal Protrusionmentioning

confidence: 99%

Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

Hadjivasiliou

Moore

McIntosh

et al. 2019

Preprint

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During early spinal cord development, neurons of particular subtypes differentiate with a sparse periodic pattern while later neurons differentiate in the intervening space to eventually produce continuous columns of similar neurons. The mechanisms that regulate this spatiotemporal pattern are unknown. In vivo imaging of zebrafish reveals differentiating spinal neurons transiently extend two long protrusions along the basal surface of the spinal cord prior to axon initiation. These protrusions express Delta protein consistent with the possibility they influence Notch signalling at a distance of several cell diameters. Experimental reduction of laminin expression leads to smaller protrusions and shorter distances between differentiating neurons. The experimental data and a theoretical model support the proposal that the pattern of neuronal differentiation is regulated by transient basal protrusions that deliver temporally controlled lateral inhibition mediated at a distance. This work uncovers novel, stereotyped protrusive activity of new-born neurons that organizes long distance spatiotemporal patterning of differentiation.

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“…The NOTCH signaling pathway is vitally involved in most cell differentiation and proliferation processes during both developmental and adult stages [ 1 , 2 , 3 ]. Mammals possess four NOTCH receptors and five canonical ligands (JAG (JAGGED canonical NOTCH ligand) 1 and 2, and DLL (DELTA-Like Canonical NOTCH Ligand) 1, 3, and 4) [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

NOTCH Receptors and DLK Proteins Enhance Brown Adipogenesis in Mesenchymal C3H10T1/2 Cells

Rodríguez-Cano

González-Gómez

Sánchez-Solana

et al. 2020

Cells

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The NOTCH family of receptors and ligands is involved in numerous cell differentiation processes, including adipogenesis. We recently showed that overexpression of each of the four NOTCH receptors in 3T3-L1 preadipocytes enhances adipogenesis and modulates the acquisition of the mature adipocyte phenotype. We also revealed that DLK proteins modulate the adipogenesis of 3T3-L1 preadipocytes and mesenchymal C3H10T1/2 cells in an opposite way, despite their function as non-canonical inhibitory ligands of NOTCH receptors. In this work, we used multipotent C3H10T1/2 cells as an adipogenic model. We used standard adipogenic procedures and analyzed different parameters by using quantitative-polymerase chain reaction (qPCR), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), luciferase, Western blot, and metabolic assays. We revealed that C3H10T1/2 multipotent cells show higher levels of NOTCH receptors expression and activity and lower Dlk gene expression levels than 3T3-L1 preadipocytes. We found that the overexpression of NOTCH receptors enhanced C3H10T1/2 adipogenesis levels, and the overexpression of NOTCH receptors and DLK (DELTA-like homolog) proteins modulated the conversion of cells towards a brown-like adipocyte phenotype. These and our prior results with 3T3-L1 preadipocytes strengthen the idea that, depending on the cellular context, a precise and highly regulated level of global NOTCH signaling is necessary to allow adipogenesis and determine the mature adipocyte phenotype.

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Modeling the Notch Response

Cited by 24 publications

References 53 publications

Basal Protrusions Mediate Spatiotemporal Patterns of Spinal Neuron Differentiation

Basal Protrusions Mediate Spatiotemporal Patterns of Spinal Neuron Differentiation

Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation

NOTCH Receptors and DLK Proteins Enhance Brown Adipogenesis in Mesenchymal C3H10T1/2 Cells

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