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. 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. 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. We assay the rates of division and whether there is anisotropic growth produced by biases in the division orientation or cell movement and integrate the data into mathematical models that describe 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.

Although the molecular and cellular mechanisms of neural tube development are evolutionarily conserved between vertebrates, the pace at which these operate varies considerably between species. The differentiation of motor neurons takes less than a day in zebrafish, 3-4 days in mouse and around 2 weeks in human. To investigate this difference in tempo we are taking advantage of access to human embryos and the in vitro recapitulation of in vivo developmental programs using the directed differentiation of human and mouse embryonic stem cells. Changes in protein stability between mouse and human correlate with developmental tempo, such that slower temporal progression in human corresponded to increased protein stability. This suggests an explanation for the substantial variation in the tempo of development between species. We are now interested in testing this hypothesis and understanding how species-specific rates of protein turnover are controlled.

SELECTED PUBLICATIONS

  • Teresa Rayon, Despina Stamataki, Ruben Perez-Carrasco, Lorena Garcia-Perez, Christopher Barrington, Manuela Melchionda, Katherine Exelby, Victor Tybulewicz, Elizabeth M. C. Fisher, James Briscoe (2020)
    Species-specific developmental timing is associated with global differences in protein stability in mouse and human
    bioRxiv 2019.12.29.889543
  • Guerrero P, Perez-Carrasco R, Zagorski M, Page D, Kicheva A, Briscoe J, Page KM. (2019)
    Neuronal differentiation influences progenitor arrangement in the vertebrate neuroepithelium.
    Development. pii: dev.176297. doi: 10.1242/dev.176297. PubMed abstract
  • Ebisuya M, Briscoe J. (2018)
    What does time mean in development?
    Development 145. pii: dev164368 PubMed abstract
  • Zagorski, M; Tabata, Y; Brandenberg, N; Lutolf, MP; Tkačik, G; Bollenbach, T; Briscoe, J and Kicheva, A (2017)
    Decoding of position in the developing neural tube from antiparallel morphogen gradients.
    Science 356, 1379-1383 PubMed abstract
  • Kicheva, A; Bollenbach, T; Ribeiro, A; Valle, HP; Lovell-Badge, R; Episkopou, V and Briscoe, J (2014)
    Coordination of progenitor specification and growth in mouse and chick spinal cord.
    Science 345, 1254927 PubMed abstract