Role of mechanical morphogenesis in the development and evolution of the neocortex

Abstract

During the short period of brain development, nature is able to build the only system we know capable of producing cognition, language, creativity, and consciousness. The neocortex-the outermost layer of the mammalian cerebrum-appears to be the biological substrate of these abilities. Its development requires not only the precise placement and wiring of billions of cells, but also the implementation of mechanisms to ensure a viable cognition despite sometimes dramatic perturbations. Today, this remarkably complex organisation is thought to be genetically encoded, and further refined by activity-dependent processes. We propose that mechanical morphogenesis-the capacity of homogeneously growing elastic tissue to produce complex shapes-can also play an important role. Out of homogeneous growth, mechanical morphogenesis can induce the segregation of the neocortex into mechanical and geometric modules-the neocortical folds. Through the feedback of physical forces on developing tissue, these modules can influence the differentiation and wiring of the neocortex, having a causal role on neocortical development, and providing adaptable and robust units for its evolution.

Brain charts for the human lifespan

“…Such standards for human brain measurement have not yet materialized from decades of neuroimaging research, probably owing to the challenges of integrating MRI data across multiple, methodologically diverse studies targeting distinct developmental epochs and clinical conditions 13 . For example, the perinatal period is rarely incorporated in analysis of age-related brain changes, despite evidence that early biophysical and molecular processes powerfully influence life-long neurodevelopmental trajectories 14 , 15 and vulnerability to psychiatric disorders 3 . Primary case–control studies are usually focused on a single disorder despite evidence of trans-diagnostically shared risk factors and pathogenic mechanisms, especially in psychiatry 16 , 17 .…”

Evolution of neocortical folding: A phylogenetic comparative analysis of MRI from 34 primate species

“…Once neocortices are fully folded, the following slow decrease in fold wavelength could be related to frequency doublingthe formation of folds within foldsas observed in swelling gel experiments (Mora and Boudaoud, 2006). Neocortical mechanics could lead to the formation of stable neuroanatomical modulesthe foldswhich could then become the basis for the adaptation and selection of advantageous cytoarchitectonic, connective and functional organisations, a kind of mechanical canalisation process (Waddington 1942, Müller 2007, Foubet et al 2018, Heuer and Toro 2019. A future analysis of fold wavelength and thickness, potentially local instead of only global, should allow us to better understand this relationship across and within species.…”

Ephrin-B2 Paces Neuronal Production in the Developing Neocortex

“…Indeed, tissue crowding or mechanical stretch have been shown to regulate cell proliferation in other contexts [30] and mechanical morphogenesis is now being recognized as a driver of neocortex development and evolution [31]. Another important question that will have to be addressed in the future is whether neurons that are generated in an inappropriate time-window upon compensation are fully functional and correctly integrated into neuronal circuits.…”