Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern

Andrew K. Lawton, Tyler Engstrom, Daniel Rohrbach, Masaaki Omura, Daniel H. Turnbull, Jonathan Mamou, Teng Zhang, Jennifer M Schwarz, Alexandra L. Joyner

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Models based in differential expansion of elastic material, axonal constraints, directed growth, or multi-phasic combinations have been proposed to explain brain folding. However, the cellular and physical processes present during folding have not been defined. We used the murine cerebellum to challenge folding models with in vivo data. We show that at folding initiation differential expansion is created by the outer layer of proliferating progenitors expanding faster than the core. However, the stiffness differential, compressive forces, and emergent thickness variations required by elastic material models are not present. We find that folding occurs without an obvious cellular pre-pattern, that the outer layer expansion is uniform and fluid-like, and that the cerebellum is under radial and circumferential constraints. Lastly, we find that a multi-phase model incorporating differential expansion of a fluid outer layer and radial and circumferential constraints approximates the in vivo shape evolution observed during initiation of cerebellar folding.

Original languageEnglish (US)
JournaleLife
Volume8
DOIs
StatePublished - Apr 16 2019

Fingerprint

Cerebellum
Physical Phenomena
Fluids
Brain
Growth
Stiffness

Keywords

  • brain Folding
  • cerebellum
  • developmental biology
  • differential expansion
  • fluidity
  • morphogenesis
  • mouse
  • multi-phase model
  • physics of living systems

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Lawton, A. K., Engstrom, T., Rohrbach, D., Omura, M., Turnbull, D. H., Mamou, J., ... Joyner, A. L. (2019). Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern. eLife, 8. https://doi.org/10.7554/eLife.45019

Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern. / Lawton, Andrew K.; Engstrom, Tyler; Rohrbach, Daniel; Omura, Masaaki; Turnbull, Daniel H.; Mamou, Jonathan; Zhang, Teng; Schwarz, Jennifer M; Joyner, Alexandra L.

In: eLife, Vol. 8, 16.04.2019.

Research output: Contribution to journalArticle

Lawton, Andrew K. ; Engstrom, Tyler ; Rohrbach, Daniel ; Omura, Masaaki ; Turnbull, Daniel H. ; Mamou, Jonathan ; Zhang, Teng ; Schwarz, Jennifer M ; Joyner, Alexandra L. / Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern. In: eLife. 2019 ; Vol. 8.
@article{b9373a8b80cc40de84876948c0f2d492,
title = "Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern",
abstract = "Models based in differential expansion of elastic material, axonal constraints, directed growth, or multi-phasic combinations have been proposed to explain brain folding. However, the cellular and physical processes present during folding have not been defined. We used the murine cerebellum to challenge folding models with in vivo data. We show that at folding initiation differential expansion is created by the outer layer of proliferating progenitors expanding faster than the core. However, the stiffness differential, compressive forces, and emergent thickness variations required by elastic material models are not present. We find that folding occurs without an obvious cellular pre-pattern, that the outer layer expansion is uniform and fluid-like, and that the cerebellum is under radial and circumferential constraints. Lastly, we find that a multi-phase model incorporating differential expansion of a fluid outer layer and radial and circumferential constraints approximates the in vivo shape evolution observed during initiation of cerebellar folding.",
keywords = "brain Folding, cerebellum, developmental biology, differential expansion, fluidity, morphogenesis, mouse, multi-phase model, physics of living systems",
author = "Lawton, {Andrew K.} and Tyler Engstrom and Daniel Rohrbach and Masaaki Omura and Turnbull, {Daniel H.} and Jonathan Mamou and Teng Zhang and Schwarz, {Jennifer M} and Joyner, {Alexandra L.}",
year = "2019",
month = "4",
day = "16",
doi = "10.7554/eLife.45019",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - Cerebellar folding is initiated by mechanical constraints on a fluid-like layer without a cellular pre-pattern

AU - Lawton, Andrew K.

AU - Engstrom, Tyler

AU - Rohrbach, Daniel

AU - Omura, Masaaki

AU - Turnbull, Daniel H.

AU - Mamou, Jonathan

AU - Zhang, Teng

AU - Schwarz, Jennifer M

AU - Joyner, Alexandra L.

PY - 2019/4/16

Y1 - 2019/4/16

N2 - Models based in differential expansion of elastic material, axonal constraints, directed growth, or multi-phasic combinations have been proposed to explain brain folding. However, the cellular and physical processes present during folding have not been defined. We used the murine cerebellum to challenge folding models with in vivo data. We show that at folding initiation differential expansion is created by the outer layer of proliferating progenitors expanding faster than the core. However, the stiffness differential, compressive forces, and emergent thickness variations required by elastic material models are not present. We find that folding occurs without an obvious cellular pre-pattern, that the outer layer expansion is uniform and fluid-like, and that the cerebellum is under radial and circumferential constraints. Lastly, we find that a multi-phase model incorporating differential expansion of a fluid outer layer and radial and circumferential constraints approximates the in vivo shape evolution observed during initiation of cerebellar folding.

AB - Models based in differential expansion of elastic material, axonal constraints, directed growth, or multi-phasic combinations have been proposed to explain brain folding. However, the cellular and physical processes present during folding have not been defined. We used the murine cerebellum to challenge folding models with in vivo data. We show that at folding initiation differential expansion is created by the outer layer of proliferating progenitors expanding faster than the core. However, the stiffness differential, compressive forces, and emergent thickness variations required by elastic material models are not present. We find that folding occurs without an obvious cellular pre-pattern, that the outer layer expansion is uniform and fluid-like, and that the cerebellum is under radial and circumferential constraints. Lastly, we find that a multi-phase model incorporating differential expansion of a fluid outer layer and radial and circumferential constraints approximates the in vivo shape evolution observed during initiation of cerebellar folding.

KW - brain Folding

KW - cerebellum

KW - developmental biology

KW - differential expansion

KW - fluidity

KW - morphogenesis

KW - mouse

KW - multi-phase model

KW - physics of living systems

UR - http://www.scopus.com/inward/record.url?scp=85064947606&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064947606&partnerID=8YFLogxK

U2 - 10.7554/eLife.45019

DO - 10.7554/eLife.45019

M3 - Article

VL - 8

JO - eLife

JF - eLife

SN - 2050-084X

ER -