Mechanobiology of neural development

Abstract

As the brain develops, proliferating cells organize into structures, differentiate, migrate, extrude long processes, and connect with other cells. These biological processes produce mechanical forces that further shape cellular dynamics and organ patterning. A major unanswered question in developmental biology is how the mechanical forces produced during development are detected and transduced by cells to impact biochemical and genetic programs of development. This gap in knowledge stems from a lack of understanding of the molecular players of cellular mechanics and an absence of techniques for measuring and manipulating mechanical forces in tissue. In this review article, we examine recent advances that are beginning to clear these bottlenecks and highlight results from new approaches that reveal the role of mechanical forces in neurodevelopmental processes.

Keywords: Biomechanics; Brain morphogenesis; Developmental biology; Mechanical forces; Mechanotransduction; Neural development.

Figure 1.. Mechanotransduction in the developing brain.

(A) The developing brain experiences a variety of mechanical cues. Left panels show a schematic of a coronal cross section of half of the developing brain, and the fluid-based forces, hydrostatic pressure (upper left) and shear flow (lower left) impinging against cells that line the ventricles. Tissue stiffness (upper right) is modulated by extracellular matrix components or by cellular density. The actomyosin cytoskeleton (lower right) connects to the extracellular matrix through focal adhesions and is integral to cellular mechanotransduction during development. CSF = cerebrospinal fluid, ECM = extracellular matrix. (B) The molecules and cellular structures involved in the mechanotransduction in the developing neuroepithelium. ap = apical border.

Figure 2.. Timeline of mechanical events during neural development

(A) The neural plate bends at three points, called hinge points (asterisks), and closes to form the neural tube.(B) Neural crest cells migrate away from the closed neural tube to form a variety of structures. (C) Neural stem/progenitor cells (NSPCs) differentiate into neurons, astrocytes, and oligodendrocytes. (D) Newly-formed neurons migrate radially or tangentially to their final destination. (E) Axons extend from the newborn neurons to form connections throughout the developing brain. (F) In some mammals including humans, the cortex folds to increase cortical surface area.