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 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 and chick embryos and mouse and human embryonic stem cells.
- Sagner A, Briscoe J (2017)
Morphogen interpretation: concentration, time, competence, and signaling dynamics.
Wiley Interdiscip Rev Dev Biol. doi: 10.1002/wdev.271 PubMed abstract
- Briscoe, J and Small, S (2015)
Morphogen rules: design principles of gradient-mediated embryo patterning.
Development 142, 3996-4009 PubMed abstract
- Gouti, M; Metzis, V and Briscoe, J (2015)
The route to spinal cord cell types: a tale of signals and switches.
Trends in Genetics 31, 282-289 PubMed abstract
- Kicheva, A and Briscoe, J (2015)
Developmental pattern formation in phases.
Trends in Cell Biology 25, 579-591 PubMed abstract