How do complex tissues of multicellular organisms develop in a precise and reproducible manner from initially indistinguishable cells?

In most tissues 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? How do these signals regulate gene expression and how is the growth, patterning and morphological elaboration of the spinal cord coordinated? What is the underlying logic of the mechanisms and how does this explain the spatial and temporal dynamics of pattern formation?

To address these questions, we are taking an interdisciplinary approach involving biologists, physicists and computer scientists.

Our focus is on the signalling mechanisms, the transcriptional programmes, and the cellular processes that pattern the neural tube, the region of the forming nervous that goes on to become the spinal cord.

The neural tube arises from progenitor cells in the posterior of embryos. These cells fuel axis elongation and the formation of the body axis by generating the tissues that comprise the trunk, including the neural tube. In the neural tube, secreted molecules, such as Sonic Hedgehog (Shh), form extracellular gradients that govern pattern formation, tissue growth, and morphogenesis. These work by regulating the expression of sets of genes, notably transcription factors, that control the identity, proliferation and behaviour of neural progenitors.

Using a range of molecular, imaging and modelling approaches that combine single cell resolution dynamic assays of signalling, cell fate specification, gene regulation and growth we are examining how 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 analyse the interdependence between different aspects of pattern formation.

For our experimental studies we use mouse, chick and human embryos and mouse and human embryonic stem cells.

SELECTED REVIEWS

  • Thomas J.R. Frith, James Briscoe, Giulia L.M. Boezio (2024)
    From signalling to form: the coordination of neural tube patterning
    Current Topics in Developmental Biology Vertebrate Pattern Formation 159:168-231 Abstract
  • Kicheva A, Briscoe J. (2023)
    Control of Tissue Development by Morphogens.
    Annual Rev Cell Dev Biol. doi: 10.1146/annurev-cellbio-020823-011522 Abstract
  • Briscoe J, Marín O. (2020)
    Looking at neurodevelopment through a big data lens.
    Science 369(6510):eaaz8627 Abstract