As the brain tube seals during development, embryonic cerebrospinal fluid (eCSF) creates pressure inside the brain. Although much is known about the chemical morphogens involved in brain morphogenesis, few studies have focused on the physical forces that contribute to the shape of the early brain. Now, Kara Garcia and colleagues use a quantitative, mathematical modelling approach to explain how the chicken cerebral hemispheres develop under different experimental conditions. First, the researchers measure proliferation, geometric changes and eCSF pressure during development of the telencephalic hemispheres. They find that eCSF pressure serves as a key regulator of cerebral hemisphere size. The authors also show that varying eCSF pressure and mechanical feedback influences tangential growth, but not radial growth, suggesting that these are two distinct processes. By integrating both mechanical input and morphogen activity, the authors’ computational model recapitulates phenotypes seen in experimental conditions, such as when mechanical forces are altered by removing surrounding tissue or by ablation of morphogen signalling. Taken together, these results support a model of chemomechanical feedback in which the interaction of molecular and mechanical signals influences embryonic hemisphere development to shape the brain.
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