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.
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. These parameters are 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.
- 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
- Kicheva, A and Briscoe, J (2015)
Developmental pattern formation in phases.
Trends in Cell Biology 25, 579-591 PubMed abstract