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

• Published in: eLife Vol. 8
• Main Authors: Lawton, Andrew K, Engstrom, Tyler, Rohrbach, Daniel, Omura, Masaaki, Turnbull, Daniel H, Mamou, Jonathan, Zhang, Teng, Schwarz, J M, Joyner, Alexandra L
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 16-04-2019; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animal models; Animals; Biophysical Phenomena; Brain; brain Folding; Cerebellum; Cerebellum - anatomy & histology; Cerebellum - growth & development; Cognition; Developmental Biology; differential expansion; fluidity; Human development; Mechanical properties; Mechanics; Mice; Models, Biological; morphogenesis; multi-phase model; Organogenesis; Physics of Living Systems; Physiological aspects; Scientists; United States; New York; United States > US; brain Folding; mouse; fluidity; morphogenesis; multi-phase model; developmental biology; differential expansion; physics of living systems; cerebellum
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.45019

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.