Now out on bioRxiv: https://doi.org/10.1101/2024.01.12.575349, using chicken embryos as a model system, we investigated how the embryonic brain expands and departs in morphology from the spinal cord early in development.
The neural tube is the embryonic precursor of the central nervous system and has a positive fluid pressure within its lumen (Desmond et al. 2005). By perturbing lumen pressure early in development, we found that it drives thinning of the hindbrain dorsal tissue and brain expansion, whilst the spinal cord resists the pressure and holds its shape.
We investigated the mechanical properties of the hindbrain and spinal cord using ferrofluid droplets, theoretical modelling and found that the dorsal hindbrain is more fluid than the dorsal spinal cord prior to brain expansion.
Why is this? We investigated 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.
Neural crest cells use matrix metalloproteases to remodel the matrix as they undergo an epithelial-to-mesenchymal transition and become migratory. We blocked the activity of matrix metalloproteases and found that brain expansion was inhibited suggesting matrix remodelling played a key role in fluidising the dorsal hindbrain tissue, allowing it to deform under lumen pressure.
By grafting small patches of cells from the dorsal hindbrain to the spinal cord of early embryos, we found that dorsal hindbrain cells were sufficient to create a brain-like morphology with a thinned out dorsal roof in the spinal cord.
This leads us to propose a model of brain and spinal cord shape divergence, where differential mechanical properties regulated by neural crest mediated matrix remodelling facilitate hindbrain dorsal tissue deformation under a positive neural tube lumen pressure.
