James Briscoe group

Neural Tube Development

We study how the central nervous system (CNS) is formed in embryos. Despite its complexity, the CNS is assembled in a remarkably reproducible 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 of the development of the spinal cord as well as shed light on diseased and damaged nervous systems. In turn, we hope this will help in the development of therapies for these conditions.

Ventral neural tube patterning by graded Shh signalling

Ventral neural tube patterning by graded Shh signalling

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The embryonic development of the neural tube provides an example of one of the fundamental questions in biology: how do complex tissues of multicellular organisms develop in a precise and reproducible manner from initially indistinguishable cells? In most tissues, including the neural tube, signals – termed morphogens – act as positional cues to control cell fate specification by regulating the transcriptional programme of responding cells.

How do cells receive and interpret these signals? Which genes respond to these signals and how do these coordinate the growth, patterning and morphological elaboration of the neural tube? What is the underlying logic of the transcriptional network and how does this control the spatial and temporal dynamics of pattern formation? To address these questions, we are taking an interdisciplinary approach involving biologists, physicists and computer scientists to investigate these questions.

Our focus is on the signalling mechanisms and transcriptional programme that pattern the neural tube. In ventral regions of the caudal neural tube, the secreted molecule Sonic Hedgehog (Shh) forms an extracellular gradient that governs pattern formation and tissue growth.

It does this by regulating the expression of a set of genes, notably transcription factors, which control the identity and proliferation of neural progenitors. Using a range of molecular, imaging and modelling approaches that combine single cell resolution dynamic assays of morphogen signaling, cell fate specification, gene regulation and growth we are examining how the gradient of Shh signalling is perceived and interpreted by cells to control gene expression and cell behaviour.

We are developing novel computational tools and dynamical systems models to obtain a comprehensive view of neural tube development and to analyze the interdependence between different aspects of pattern formation. For our experimental studies we use a range models including mouse, chick, zebrafish embryos and mouse and human embryonic stem cells.

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