Now out on bioRxiv: https://doi.org/10.1101/2024.01.12.575349, we use chicken embryos to investigate how the embryonic brain expands and departs in morphology from the spinal cord early in development.
The neural tube, the embryonic precursor of the central nervous system, has a positive internal fluid pressure (Desmond et al. 2005). By modulating the pressure we found that it drives hindbrain dorsal tissue thinning and expansion, whilst the spinal cord holds its shape. To understand why these different regions of the connected neural tube show a different response to lumen pressure, we investigated the material properties of the hindbrain and spinal cord in collaboration with the Hannezo lab at IST, Vienna and the Franze lab at PDN, Cambridge. Using ferrofluid droplets, theoretical modelling and atomic force microscopy, we found that the dorsal hindbrain is more fluid than the dorsal spinal cord prior to brain expansion. Why might this be? We looked into extracellular matrix organisation as it plays an important role in determining a tissue’s material properties and found that matrix organisation differed between the dorsal hindbrain and spinal cord. This difference in matrix organisation occurred within the snail2+ premigratory neural crest domain of the neural tube. Blocking the activity of matrix metalloproteases used by neural crest cells use to remodel the matrix inhibited brain expansion. This suggested that matrix remodelling played a key role in fluidising the dorsal hindbrain, allowing it to deform under lumen pressure. Finally, by grafting a small patch of cells from the dorsal hindbrain to the dorsal spinal cord in early embryos and allowing them to develop, we found that dorsal hindbrain cells were sufficient to create a brain-like morphology with a thinned out dorsal roof in the spinal cord.
Altogether, this leads us to propose a model of early brain and spinal cord shape divergence, where differential mechanical properties regulated by neural crest mediated matrix remodelling facilitate brain expansion relative to the spinal cord under a positive neural tube lumen pressure.