Shaping the Nervous System: Mechanical Drivers of Neurulation and Neurogenesis

The formation of the nervous system is a remarkable process that relies on the coordinated interplay of cellular programs, molecular signaling, and mechanical forces. Neurulation, the folding of the neural plate into the neural tube, and subsequent neurogenesis are foundational events that establish the architecture and functionality of the brain and spinal cord. While genetic and biochemical cues provide instructive signals for cell fate and patterning, mechanical forces are increasingly recognized as essential drivers that shape tissue morphology, guide cellular behaviors, and influence circuit formation.During neurulation, coordinated cell shape changes, apical constriction, and cytoskeletal contractility generate the forces necessary for bending and closure of the neural tube. Interactions between epithelial cells, mediated by adhesion molecules and actomyosin networks, ensure tissue integrity and proper morphogenesis. Disruptions in these mechanical processes can lead to neural tube defects, highlighting the critical role of biophysical cues alongside molecular regulation.Following neural tube formation, neurogenesis relies on tightly controlled progenitor proliferation, differentiation, and migration. Cellular mechanics, including cytoskeletal dynamics, cell polarity, and intercellular tension, interact with extracellular matrix properties and tissue stiffness to influence cell division orientation, neuronal subtype specification, and cortical layer formation. Migrating neurons rely on both mechanical guidance from radial glia and biochemical gradients of growth factors and morphogens, illustrating the complex interplay between physical and molecular cues in neural development.Mechanotransduction pathways, including stretch-activated ion channels and integrin-mediated adhesion complexes, translate physical forces into intracellular signaling that regulates gene expression and cellular behaviors. Emerging studies using live imaging, micropatterned substrates, and organoid models reveal how variations in tissue stiffness, cytoskeletal tension, and cell density orchestrate the formation of functional neural circuits.Understanding the mechanical drivers of neurulation and neurogenesis offers profound insights into developmental biology, disease mechanisms, and regenerative medicine. Disruptions in these processes contribute to congenital disorders such as spina bifida, lissencephaly, and microcephaly, while engineered microenvironments mimicking physiological mechanical cues provide strategies for stem cell differentiation and neural tissue engineering.Key Research Areas• Cellular and cytoskeletal mechanisms driving neural tube folding and closure• Role of tissue tension and adhesion in shaping neural progenitor behavior• Influence of extracellular matrix mechanics on neuronal differentiation and migration• Mechanotransduction pathways regulating gene expression during neurogenesis• Interplay between glial scaffolds, migrating neurons, and mechanical cues in circuit formation Topic editors: Eirini Maniou, Manuela Ceccarelli Source: https://www.frontiersin.org/research-topics/76759/shaping-the-nervous-system-mechanical-drivers-of-neurulation-and-neurogenesis