Neural tube development

Lead Research Organisation: The Francis Crick Institute

Abstract

We study how the central nervous system (CNS) is formed in embryos. Despite its complexity, the CNS is assembled in a remarkably precise and reliable manner. This precision is necessary for the wiring of nerves into the functional neural circuits that gives the CNS its function. Our research focuses on the spinal cord, which is the part of the CNS that contains the nerves that allow us to sense our environment and respond to it by moving muscles. Our goal is to identify the genes involved in spinal cord development and determine how they work to produce and organize the different types of nerve cells found in this part of the CNS. This will contribute to understanding the development of the spinal cord as well as shed light on diseased and damaged nervous systems.

Technical Summary

This work was supported by the Francis Crick Institute which receives its core funding from the UK Medical Research Council (FC001000), the Wellcome Trust (FC001000),and Cancer Research UK (FC001000).

A central problem in biology and key to realising the potential of regenerative medicine is understanding the mechanisms that produce and organize cells in the complex tissues of an embryo. In broad terms, initially uncommitted progenitors acquire their fate in response to signals that control transcriptional programmes. These programmes drive developing cells through spatial and temporal successions of cell states that gradually refine cell identity. How these states are established and cell fate decisions implemented is poorly understood. To address this we use an experimentally tractable system – the formation of defined populations of progenitors in the vertebrate spinal cord. We will take an interdisciplinary approach. We have developed in vitro differentiation systems that use embryonic stem cells to recapitulate the in vivo development of the spinal cord. We have embraced new technologies that provide unprecedented ability to manipulate and assay single cells. Finally, we have established interdisciplinary collaborations to develop computational tools and construct data driven mathematical models. Using these approaches, alongside established embryological methods, we have established a platform for manipulating and analysing mechanisms by which the multipotent progenitors that form the spinal cord acquire specific identities. We will identify the rules by which cells make decisions and we will define the design logic and network architectures that lead to distinct cell fate choices. The ability to: (i) follow the trajectory of a cell as it transitions to a specific neuronal subtype in vivo; (ii) manipulate the process in vitro and in vivo; and (iii) model it in silico, offers a unique system for understanding organogenesis. Together these approaches will provide the knowledge and technical foundations for rational, predictive tissue engineering of the spinal cord.

Publications

10 25 50