Wall stress enhanced exocytosis of extracellular vesicles as a possible mechanism of left-right symmetry-breaking in vertebrate development

J. Solowiej-Wedderburn, D. J. Smith, S. S. Lopes, T. D. Montenegro-Johnson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

In certain vertebrate species, the developing embryo breaks left-right symmetry in a transient organising structure: the “Left-Right Organiser” (LRO) known as the “node” in mice, and “Kupffer's vesicle” in fish. Directional cilia-driven flow is integral to this symmetry-breaking process, however the mechanism by which this flow is translated into an asymmetric signal remains contested; the principal theories are either flow transport of vesicles containing morphogens, or flow mechanosensing by cilia. Whilst some recent work favours the morphogen theory, other findings seem to support mechanosensing. In this study, we consider a hypothesis whereby the cilia themselves drive the release of morphogen-carrying extracellular vesicles (EVs) into the LRO; namely, that fluid stresses on the cell membrane induce/enhance exocytosis of EVs. Using a mathematical model, we calculate significant wall normal and shear stresses for a range of typical cilium parameter values comparable to levels capable of enhancing exocytosis. This mechanism may be able to reconcile the apparently conflicting experimental evidence.

LanguageEnglish
Pages220-226
Number of pages7
JournalJournal Of Theoretical Biology
Volume460
DOIs
Publication statusPublished - 7 Jan 2019

Fingerprint

exocytosis
Cilia
Exocytosis
Vesicles
cilia
Cell membranes
Symmetry Breaking
Fish
Vertebrates
Shear stress
vertebrates
Mathematical models
Fluids
Transport Vesicles
Embryo
Shear Stress
shear stress
cell membranes
Mouse
embryo (animal)

Keywords

  • Cilia-driven flow
  • Left-right symmetry-breaking

Cite this

@article{2f8c8b7c968a4bd39d48b8972678625b,
title = "Wall stress enhanced exocytosis of extracellular vesicles as a possible mechanism of left-right symmetry-breaking in vertebrate development",
abstract = "In certain vertebrate species, the developing embryo breaks left-right symmetry in a transient organising structure: the “Left-Right Organiser” (LRO) known as the “node” in mice, and “Kupffer's vesicle” in fish. Directional cilia-driven flow is integral to this symmetry-breaking process, however the mechanism by which this flow is translated into an asymmetric signal remains contested; the principal theories are either flow transport of vesicles containing morphogens, or flow mechanosensing by cilia. Whilst some recent work favours the morphogen theory, other findings seem to support mechanosensing. In this study, we consider a hypothesis whereby the cilia themselves drive the release of morphogen-carrying extracellular vesicles (EVs) into the LRO; namely, that fluid stresses on the cell membrane induce/enhance exocytosis of EVs. Using a mathematical model, we calculate significant wall normal and shear stresses for a range of typical cilium parameter values comparable to levels capable of enhancing exocytosis. This mechanism may be able to reconcile the apparently conflicting experimental evidence.",
keywords = "Cilia-driven flow, Left-right symmetry-breaking",
author = "J. Solowiej-Wedderburn and Smith, {D. J.} and Lopes, {S. S.} and Montenegro-Johnson, {T. D.}",
year = "2019",
month = "1",
day = "7",
doi = "10.1016/j.jtbi.2018.10.015",
language = "English",
volume = "460",
pages = "220--226",
journal = "Journal Of Theoretical Biology",
issn = "0022-5193",
publisher = "Elsevier Science B.V., Amsterdam.",

}

Wall stress enhanced exocytosis of extracellular vesicles as a possible mechanism of left-right symmetry-breaking in vertebrate development. / Solowiej-Wedderburn, J.; Smith, D. J.; Lopes, S. S.; Montenegro-Johnson, T. D.

In: Journal Of Theoretical Biology, Vol. 460, 07.01.2019, p. 220-226.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Wall stress enhanced exocytosis of extracellular vesicles as a possible mechanism of left-right symmetry-breaking in vertebrate development

AU - Solowiej-Wedderburn, J.

AU - Smith, D. J.

AU - Lopes, S. S.

AU - Montenegro-Johnson, T. D.

PY - 2019/1/7

Y1 - 2019/1/7

N2 - In certain vertebrate species, the developing embryo breaks left-right symmetry in a transient organising structure: the “Left-Right Organiser” (LRO) known as the “node” in mice, and “Kupffer's vesicle” in fish. Directional cilia-driven flow is integral to this symmetry-breaking process, however the mechanism by which this flow is translated into an asymmetric signal remains contested; the principal theories are either flow transport of vesicles containing morphogens, or flow mechanosensing by cilia. Whilst some recent work favours the morphogen theory, other findings seem to support mechanosensing. In this study, we consider a hypothesis whereby the cilia themselves drive the release of morphogen-carrying extracellular vesicles (EVs) into the LRO; namely, that fluid stresses on the cell membrane induce/enhance exocytosis of EVs. Using a mathematical model, we calculate significant wall normal and shear stresses for a range of typical cilium parameter values comparable to levels capable of enhancing exocytosis. This mechanism may be able to reconcile the apparently conflicting experimental evidence.

AB - In certain vertebrate species, the developing embryo breaks left-right symmetry in a transient organising structure: the “Left-Right Organiser” (LRO) known as the “node” in mice, and “Kupffer's vesicle” in fish. Directional cilia-driven flow is integral to this symmetry-breaking process, however the mechanism by which this flow is translated into an asymmetric signal remains contested; the principal theories are either flow transport of vesicles containing morphogens, or flow mechanosensing by cilia. Whilst some recent work favours the morphogen theory, other findings seem to support mechanosensing. In this study, we consider a hypothesis whereby the cilia themselves drive the release of morphogen-carrying extracellular vesicles (EVs) into the LRO; namely, that fluid stresses on the cell membrane induce/enhance exocytosis of EVs. Using a mathematical model, we calculate significant wall normal and shear stresses for a range of typical cilium parameter values comparable to levels capable of enhancing exocytosis. This mechanism may be able to reconcile the apparently conflicting experimental evidence.

KW - Cilia-driven flow

KW - Left-right symmetry-breaking

UR - http://www.scopus.com/inward/record.url?scp=85055202803&partnerID=8YFLogxK

U2 - 10.1016/j.jtbi.2018.10.015

DO - 10.1016/j.jtbi.2018.10.015

M3 - Article

VL - 460

SP - 220

EP - 226

JO - Journal Of Theoretical Biology

T2 - Journal Of Theoretical Biology

JF - Journal Of Theoretical Biology

SN - 0022-5193

ER -