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.
| Language | English |
|---|---|
| Pages | 220-226 |
| Number of pages | 7 |
| Journal | Journal Of Theoretical Biology |
| Volume | 460 |
| DOIs | |
| Publication status | Published - 7 Jan 2019 |
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Keywords
- Cilia-driven flow
- Left-right symmetry-breaking
Cite this
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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 journal › Article
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 -