David Wilkinson

Neural Development Laboratory

During early stages of nervous system development in vertebrates, neural tissue is subdivided into building blocks, each with a distinct regional identity. Within these subdivisions, the proliferation and differentiation of progenitor cells is regulated in time and space to form the correct number and organisation of neuronal and glial cells.

In order for these precise patterns to form and be maintained, it is essential that cells do not migrate into inappropriate locations. Disruption of the mechanisms that regulate cell proliferation, differentiation or migration can lead to diseases such as cancer.

Our studies aim to elucidate molecular and cellular mechanisms that regulate formation of precise tissue subdivisions and patterns of differentiating cells in the vertebrate nervous system. We are analysing how signaling through Eph receptors and ephrins inhibits intermingling and establishes sharp boundaries between distinct cell populations.

In other studies, we have identified a pathway mediated by targeted protein degradation required for the onset of neuronal differentiation, and uncovered a novel mechanism underlying spatial patterning of neurogenesis involving FGF signaling from neurons.

Our experimental studies of nervous system development use the advantages of the zebrafishmodel for gene modification and imaging of cell behaviour. In addition, we utilise a combination of cell culture assays and mathematical modelling to analyse mechanisms of cell segregation and border formation.

 

Figure 1

Figure 1. Detection of hindbrain segments 3 and 5 (blue), boundary cells (red) and neurons (green) in the developing zebrafish hindbrain.

Figure 2

Figure 2. Cell culture assay for segregation of cells expressing EphB2 receptor (unlabelled) and ephrinB1 (green).

Selected publications

Terriente J, Gerety SS, Watanabe-Asaka T, Gonzalez-Quevedo R and Wilkinson DG (2012) Signaling from hindbrain boundaries regulates neuronal clustering that patterns neurogenesis. Development 139, 2978-2987.

Batlle E and Wilkinson DG (2012) Molecular mechanisms of cell segregation and boundary formation in development and tumorigenesis. Cold Spring Harb. Perspect. Biol. 4: a008227.

Gonzalez-Quevedo R, Lee Y, Poss KD and Wilkinson DG (2010) Neuronal regulation of the spatial patterning of neurogenesis. Developmental Cell 18, 136-147

David Wilkinson

david.wilkinson@crick.ac.uk
+44 (0)20 379 61638

  • Qualifications and history
  • 1983 PhD University of Leeds, Leeds, UK
  • 1983 Postdoctoral Fellow, Institute for Cancer Research, Philadelphia, USA
  • 1986 Postdoctoral Fellow, Medical Research Council National Institute for Medical Research (MRC-NIMR), London, UK
  • 1988 Group Leader, MRC-NIMR, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK