ABSTRACT An expanded brain enables the complex behaviours of vertebrates that promote their adaptation in diverse ecological niches 1–3 . Initial morphological differences between the brain and spinal cord emerge as the antero-posteriorly patterned neural plate folds to form the neural tube 4–7 during embryonic development. Following neural tube closure, a dramatic expansion of the brain diverges its shape from the spinal cord 8 , setting their distinct morphologies for further development 9,10 . How the brain and the spinal cord expand differentially remains unclear. Here, using the chicken embryo as a model, we show that the hindbrain expands through dorsal tissue thinning under a positive hydrostatic pressure from the neural tube lumen 11,12 while the dorsal spinal cord shape resists the same pressure. Using magnetic droplets and atomic force microscopy, we reveal that the dorsal tissue in the hindbrain is more fluid than in the spinal cord. The dorsal hindbrain harbours more migratory neural crest cells 13 and exhibits reduced apical actin and a disorganised laminin matrix compared to the dorsal spinal cord. Blocking the activity of neural crest-associated matrix metalloproteinases inhibited dorsal tissue thinning, leading to abnormal brain morphology. Transplanting early dorsal hindbrain cells to the spinal cord was sufficient to create a region with expanded brain-like morphology including a thinned-out roof. Our findings open new questions in vertebrate head evolution and neural tube defects, and suggest a general role of mechanical pre-pattern in creating shape differences in epithelial tubes.

Differential tissue deformability underlies shape divergence of the embryonic brain and spinal cord under fluid pressure