Susie McLaren

How does a simple tube give rise to the complex geometry of the central nervous system?

Keywords: Keywords: central nervous system, neural tube, fluid pressure, lumen pressure, tissue material properties.

The brain and spinal cord, comprising the vertebrate central nervous system, have different shapes that are crucial for their function. How these different shapes arise is not well understood. The central nervous system begins as the neural tube which has a continuous fluid-filled lumen that connects the early brain and spinal cord along the embryo anterior-posterior axis. Early on in development the neural tube closes at both ends and develops a positive internal fluid pressure. Following this the brain-forming part of the neural tube expands dramatically whilst the spinal cord-forming part maintains its shape and remains narrow.

Using a combination of mechanical perturbations and measurement of tissue material properties, we are investigating the divergence in shape of the brain and spinal cord during embryonic development and propose that it is driven by differences in the extent of tissue deformation in response to internal lumen pressure. We identify the neural crest as a key candidate for mediating this variation in tissue material properties. Our working model suggests that softening of tissue comprising the dorsal part of the early hindbrain leads to pressure-driven tissue deformation and brain expansion, whilst stiffer dorsal tissue in the early spinal cord resists deformation and maintains spinal cord shape. Overall, our findings suggest that the interaction between external forces, such as fluid pressure, and tissue material properties underlies the sculpting of the early central nervous system.

This work advances our understanding of the interplay between external forces, such as fluid pressure, and the material properties of the tissues they act on in shaping fundamental biological structures such as the central nervous system. Our current findings highlight possible new mechanisms of mechanical regulation of central nervous system morphogenesis. Additionally, this work has developed tools for quantitatively measuring lumen pressure within the developing avian embryo and is advancing methods to determine the relative stiffness of different embryonic tissues. These tools have the scope to be applied to numerous biological systems and questions, facilitating the application of physics-based theory to biological questions.

Gurdon Institute

Dr Fengzhu Xiong Lab

Figure legend: a) How does differential brain and spinal cord geometry arise from a simple tube? b) Softer tube walls allow for greater deformation under internal lumen pressure. c) We propose that neural crest-mediated ECM degradation leads to softening of the dorsal hindbrain and expansion of the hindbrain relative to the spinal cord.