James Briscoe

Developmental Dynamics Laboratory

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. 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 (Click to view larger image)

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. 

Current projects

Dynamics of Shh signalling and gene expression

Elucidation of the transcriptional network 

Coordinating patterning and growth

In vitro generation of spinal cord cells from ES cells

Visualizing gene expression

Development of the serotonergic system 

Selected publications

Anna Kicheva, Tobias Bollenbach, Ana Ribeiro, Helena Pérez Valle, Robin Lovell-Badge, Vasso Episkopou, James Briscoe (2014) Coordination of progenitor specification and growth in the chick and mouse spinal cord.  Science 345, 1577 PubMed abstract  Abstract

Mina Gouti, Anestis Tsakiridis, Filip J Wymeersch, Yali Huang, Jens Kleinjung, Valerie Wilson, and James Briscoe (2014) In Vitro Generation of Neuromesodermal Progenitors Reveals Distinct Roles for Wnt Signalling in the Specification of Spinal Cord and Paraxial Mesoderm Identity.  PLoS Biology 12, e1001937 PubMed abstract

Briscoe, J and Thérond, PP (2013) **The mechanisms of Hedgehog signalling and its roles in development and diseaseNature Reviews Molecular Cell Biology  14, 416-429 PubMed abstract

 

James Briscoe

James Briscoe

james.briscoe@crick.ac.uk
+44 (0) 20 8816 2559

  • Qualifications and history
  • 1996 PhD Imperial Cancer Research Fund/Kings College, London, UK
  • 1996 Post doctoral fellow Columbia University, New York, USA
  • 2000 Group Leader, Medical Research Council National Institute for Medical Research, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK