Mechanical Forces Orchestrate Brain Development

Mechanotransduction of environmental signals governs important cell functions during brain development. Recent discoveries have shown that disruption of brain mechanical properties during embryogenesis is associated with neurodevelopmental disorders. Thus, a better understanding of mechanobiology will also enhance our knowledge of brain disorders. The advent of new technologies will increase our ability to measure and manipulate the physical features of neuronal cells and their environment. During brain development, progenitors generate successive waves of neurons that populate distinct cerebral regions, where they settle and differentiate within layers or nuclei. While migrating and differentiating, neurons are subjected to mechanical forces arising from the extracellular matrix, and their interaction with neighboring cells. Changes in brain biomechanical properties, during its formation or aging, are converted in neural cells by mechanotransduction into intracellular signals that control key neurobiological processes. Here, we summarize recent findings that support the contribution of mechanobiology to neurodevelopment, with focus on the cerebral cortex. Also discussed are the existing toolbox and emerging technologies made available to assess and manipulate the physical properties of neurons and their environment. During brain development, progenitors generate successive waves of neurons that populate distinct cerebral regions, where they settle and differentiate within layers or nuclei. While migrating and differentiating, neurons are subjected to mechanical forces arising from the extracellular matrix, and their interaction with neighboring cells. Changes in brain biomechanical properties, during its formation or aging, are converted in neural cells by mechanotransduction into intracellular signals that control key neurobiological processes. Here, we summarize recent findings that support the contribution of mechanobiology to neurodevelopment, with focus on the cerebral cortex. Also discussed are the existing toolbox and emerging technologies made available to assess and manipulate the physical properties of neurons and their environment. family of proteins that contain a Bin/amphiphysin/Rvs (BAR) domain, which includes six subfamilies: N-BAR, BAR, F-BAR, I-BAR, PX-BAR, and BAR-PH. BAR proteins regulate the curvature of the cell membrane, and according to their structure they generate different membrane phenotypes. mammalian ATP-dependent chromatin remodeling complex that contains DNA and histone-binding domains. LEM domain-containing protein mainly localized in the inner nuclear membrane that is involved in the localization of chromatin to the nuclear periphery. fibronectin leucine rich-repeat transmembrane (FLRT1-3) family of proteins that function as cell adhesion molecules as well as chemorepellents through Unc5 receptors. highly dynamic macromolecular complex composed by hundreds of proteins including integrins, that allow transmission of force from the ECM to the actin cytoskeleton. nucleoskeletal protein that interacts with transcription factors and other lamin-associated proteins, to regulate the structure and mechanical properties of the nucleus. protein complex that physically connects the nuclear lamina with the cytoskeleton, thereby allowing the propagation of mechanotransduction events to the nucleus. set of ECM and ECM-associated proteins, also known as the extracellular matrix proteome. molecular mechanism used by cells to sense and convert external forces into biochemical and biological responses. dense protein network located below the inner surface of the nucleus, that consists mainly of lamin intermediate filaments. It provides a scaffold for the nuclear envelope, and is involved in the organization of chromatin. superfamily of cationic channels that based on sequence homology are divided into seven subfamilies: TRPA, TRPC, TRPM, TRPML, TRPN, TRPP, and TRPV. Several members are involved in mechanosensing and can be activated through mechanical forces. In D. melanogaster, the TRPN ortholog NOMPC is required for mechanotransduction.