Impulsive signaling model of cytoneme-based morphogen gradient formation
File(s)cytopunctaR.pdf (682.19 KB)
Accepted version
Author(s)
Kim, Hyunjoong
Bressloff, Paul C
Type
Journal Article
Abstract
Morphogen protein gradients play a vital role in regulating spatial pattern formation during development. The most commonly accepted mechanism of protein gradient formation involves the diffusion and degradation of morphogens from a localized source. However, there is growing experimental evidence for a direct cell-to-cell signaling mechanism via thin actin-rich cellular extensions known as cytonemes. Recent modeling studies of cytoneme-based morphogenesis in invertebrates ignore the discrete nature of vesicular transport along cytonemes, focusing on deterministic continuum models. In this paper, we develop an impulsive signaling model of morphogen gradient formation in invertebrates, which takes into account the discrete and stochastic nature of vesicular transport along cytonemes. We begin by solving a first passage time problem with sticky boundaries to determine the expected time to deliver a vesicle to a target cell, assuming that there is a 'nucleation' time for injecting the vesicle into the cytoneme. We then use queuing theory to analyze the impulsive model of morphogen gradient formation in the case of multiple cytonemes and multiple targets. In particular, we determine the steady-state mean and variance of the morphogen distribution across a one-dimensional array of target cells. The mean distribution recovers the spatially decaying morphogen gradient of previous deterministic models. However, the burst-like nature of morphogen transport can lead to Fano factors greater than unity across the array of cells, resulting in significant fluctuations at more distant target sites.
Date Issued
2019-09
Date Acceptance
2019-06-24
Citation
Physical Biology, 2019, 16 (5)
ISSN
1478-3967
Publisher
IOP Publishing
Journal / Book Title
Physical Biology
Volume
16
Issue
5
Copyright Statement
Copyright © 2019 IOP Publishing Ltd. This is an author-created, un-copyedited version of an article published in Physical Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at 10.1088/1478-3975/ab2c5a
Identifier
http://dx.doi.org/10.1088/1478-3975/ab2c5a
Publication Status
Published
Article Number
056005
Date Publish Online
2019-07-22