RT Journal Article
SR Electronic
T1 Brain folding is initiated by mechanical constraints without a cellular pre-pattern
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 382887
DO 10.1101/382887
A1 Andrew K Lawton
A1 Tyler Engstrom
A1 Daniel Rohrbach
A1 Masaaki Omura
A1 Daniel H Turnbull
A1 Jonathan Mamou
A1 Teng Zhang
A1 J. M. Schwarz
A1 Alexandra L Joyner
YR 2018
UL http://biorxiv.org/content/early/2018/08/01/382887.abstract
AB During human brain development the cerebellum and cerebral cortex fold into robust patterns that increase and compartmentalize neural circuits. Although differential expansion of elastic materials has been proposed to explain brain folding, the cellular and physical processes responsible at the time of folding have not been defined. Here we used the murine cerebellum, with 8-10 folds, as a tractable model to study brain folding. At folding initiation we considered the cerebellum as a bilayer system with a fluidlike outer layer of proliferating precursors and an incompressible core. We discovered that there is no obvious cellular pre-pattern for folding, since when folding initiates, the precursors within the outer layer have uniform sizes, shapes and proliferation, as well as a distribution of glial fibers. Furthermore, although differential expansion is created by the outer layer expanding faster than the core at folding initiation, thickness variations arise in the outer layer that are inconsistent with elastic material models. A multiphase model was applied that includes radial and circumferential tension and mechanical constraints derived from in vivo measurements. Our results demonstrate that cerebellar folding emerges from mechanical forces generated by uniform cell behaviors. We discuss how our findings apply to human cerebral cortex folding.