MRC National Institute for Medical Research, London
Science for Health
James Briscoe group project:
Coordinating patterning and growth
Neuroepithelial cells form a single-cell-layered pseudostratified epithelium that undergoes interkinetic nuclear migration. Concomitant with patterning, the neural tube grows and both symmetric (proliferative) and asymmetric (neurogenic) cell divisions take place. In addition to its role in patterning, Shh signalling promotes the proliferation and survival of neural progenitors thereby contributing to neural tube growth. We are interested in understanding how the proliferation, orientation of division, interkinetic nuclear movement and neuronal differentiation are coordinated with patterning and what role growth plays in gene expression dynamics. To address these questions we are analysing the coordination of cell proliferation and patterning and developing a model of neural tube growth.
Measuring growth dynamics
We aim to determine how the growth and patterning of the neural tube at the population level results from the collective behaviours of individual cells. To obtain the single cell resolution necessary for this, we are using clonal lineage tracing methods in mouse and chick. These data are used to determine the rates and probabilities of division and whether there is anisotropic growth produced by biases in the division orientation or cell movement. With the help of collaborators at the Cavendish Laboratories, Cambridge these parameters are being integrated into a mathematical model that describes neural tube growth. We will use these data to make experimental predictions to test and refine the model and understand the molecular basis of the coordination of growth and patterning.
Analysis of the proliferation and differentiation of neural progenitors
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Dynamics of neural tube development at cellular resolution
How is gene expression coordinated with cell division? To address this question we are combining in vivo fluorescent reporters with live imaging. We are asking how cell cycle, the movement of the cell body, division orientation and behaviour of sister cells affect neuroepithelial behaviour. In addition, we want to address whether initiation of the expression of transcription factors that define progenitor identity is associated with a particular cell cycle phase and whether there is any association between Shh signalling and cell cycle phase. Live imaging will also be used to address how closely correlated are dynamic changes in signalling levels with changes in gene expression. Understanding and quantifying this will be important for understanding how patterning precision is achieved.
Live imaging of the developing neural tube
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Selected publications
- Ulloa F, Itasaki N and Briscoe J (2007)
Inhibitory Gli3 activity negatively regulates Wnt/β-catenin signaling.
Current Biology 17, 545-50 PubMed abstract - Cayuso J, Ulloa F, Cox B, Briscoe J and Martí E (2006)
The Sonic hedgehog pathway independently controls the patterning, proliferation and survival of neuroepithelial cells by regulating Gli activity.
Development 133, 517-528 PubMed abstract
Briscoe group
Recent publications
Research projects
- Dynamics of Shh signalling and gene expression
- Coordinating patterning and growth
- Elucidation of the transcriptional network
- Visualising gene expression
- Development of the serotonergic system
Briscoe biography
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