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An expanded Notch-Delta model exhibiting long-range patterning and incorporating MicroRNA regulation

PLoS computational biology, 2014-06, Vol.10 (6), p.e1003655-e1003655 [Peer Reviewed Journal]

COPYRIGHT 2014 Public Library of Science ;COPYRIGHT 2014 Public Library of Science ;2014 Chen et al 2014 Chen et al ;2014 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Chen JS, Gumbayan AM, Zeller RW, Mahaffy JM (2014) An Expanded Notch-Delta Model Exhibiting Long-Range Patterning and Incorporating MicroRNA Regulation. PLoS Comput Biol 10(6): e1003655. doi:10.1371/journal.pcbi.1003655 ;ISSN: 1553-7358 ;ISSN: 1553-734X ;EISSN: 1553-7358 ;DOI: 10.1371/journal.pcbi.1003655 ;PMID: 24945987

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Title:
An expanded Notch-Delta model exhibiting long-range patterning and incorporating MicroRNA regulation
Author: Chen, Jerry S ; Gumbayan, Abygail M ; Zeller, Robert W ; Mahaffy, Joseph M
Nie, Qing
Subjects: Animals ; Animals, Genetically Modified ; Biology and Life Sciences ; Body Patterning - genetics ; Body Patterning - physiology ; Cell Communication - physiology ; Cellular signal transduction ; Ciona intestinalis - genetics ; Ciona intestinalis - growth & development ; Ciona intestinalis - physiology ; Computational Biology ; Computer and Information Sciences ; Computer Simulation ; Experiments ; Gene expression ; Gene Expression Regulation, Developmental ; Genetic regulation ; Genetic research ; Homeostasis ; Intracellular Signaling Peptides and Proteins - physiology ; Ligands ; Mathematical models ; Membrane Proteins - physiology ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Models, Neurological ; Monte Carlo Method ; Nervous system ; Nervous System - cytology ; Nervous System - growth & development ; Physical Sciences ; Physiological aspects ; Receptors, Notch - physiology ; RNA sequencing ; Sensory Receptor Cells - cytology ; Sensory Receptor Cells - physiology ; Signal Transduction ; Simulation ; Studies
Is Part Of: PLoS computational biology, 2014-06, Vol.10 (6), p.e1003655-e1003655
Description: Notch-Delta signaling is a fundamental cell-cell communication mechanism that governs the differentiation of many cell types. Most existing mathematical models of Notch-Delta signaling are based on a feedback loop between Notch and Delta leading to lateral inhibition of neighboring cells. These models result in a checkerboard spatial pattern whereby adjacent cells express opposing levels of Notch and Delta, leading to alternate cell fates. However, a growing body of biological evidence suggests that Notch-Delta signaling produces other patterns that are not checkerboard, and therefore a new model is needed. Here, we present an expanded Notch-Delta model that builds upon previous models, adding a local Notch activity gradient, which affects long-range patterning, and the activity of a regulatory microRNA. This model is motivated by our experiments in the ascidian Ciona intestinalis showing that the peripheral sensory neurons, whose specification is in part regulated by the coordinate activity of Notch-Delta signaling and the microRNA miR-124, exhibit a sparse spatial pattern whereby consecutive neurons may be spaced over a dozen cells apart. We perform rigorous stability and bifurcation analyses, and demonstrate that our model is able to accurately explain and reproduce the neuronal pattern in Ciona. Using Monte Carlo simulations of our model along with miR-124 transgene over-expression assays, we demonstrate that the activity of miR-124 can be incorporated into the Notch decay rate parameter of our model. Finally, we motivate the general applicability of our model to Notch-Delta signaling in other animals by providing evidence that microRNAs regulate Notch-Delta signaling in analogous cell types in other organisms, and by discussing evidence in other organisms of sparse spatial patterns in tissues where Notch-Delta signaling is active.
Publisher: United States: Public Library of Science
Language: English
Identifier: ISSN: 1553-7358
ISSN: 1553-734X
EISSN: 1553-7358
DOI: 10.1371/journal.pcbi.1003655
PMID: 24945987
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
Public Library of Science (PLoS)
ProQuest Central
DOAJ Directory of Open Access Journals

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An expanded Notch-Delta model exhibiting long-range patterning and incorporating MicroRNA regulation

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