Mechanical collaboration between the embryonic brain and the surrounding scalp tissues

During brain enlargement between embryonic day (E) 11 and E13, within the limited mouse cranial space enclosed by the scalp consisting of epidermal and preosteogenic mesenchymal layers, the angle between the pons and the medulla decreases. This raises the possibility that the scalp, upon being pushed outwardly by the brain and stretched, in return inwardly recoils to confine and fold the brain. Our stress-releasing tests showed that the scalp recoiled to shrink more extensively at E12~13 than at E15~16 and that the in vivo pre-stretch prerequisite for this recoil response depended physically on the brain (pressurization at 77~93 Pa) and on actomyosin and elastin within the scalp layers. Under non-stretched conditions, scalp cell proliferation declined, while re-stretching of the shrunken scalp rescued proliferation. In scalp-removed heads, pons–medulla folding was reduced, and the spreading of ink from the lateral ventricle to the spinal cord that occurred in scalp-intact embryos (with >5 μl injection) was lost, suggesting that the scalp plays roles in brain morphogenesis and cerebrospinal fluid homeostasis. Thus, the brain and the scalp mechanically interact and collaborate. ### Competing Interest Statement The authors have declared no competing interest.