A major open question in developmental biology is how organ size is controlled in a coordinated and robust manner. To understand this, it is necessary to understand how proliferation and differentiation are balanced, such that a tissue stops growing at the appropriate size – and that it does so at the appropriate time. Sean Megason and colleagues now seek to address this question, using live imaging and mathematical simulation of the zebrafish neural tube. They observe a correlation between nuclear position in the apico-basal plane and differentiation: pre-mitotic cells with more basally located nuclei are more likely to differentiate following division. The authors hypothesise that this is a consequence of cell packing effects: crowding at the apical surface leads both to basal displacement of cells and to subsequent differentiation. They further propose that this may be regulated by Notch signalling, which inhibits differentiation and is downregulated in cells further from the apical surface. Although the mechanism by which cell packing impacts upon differentiation remains incompletely understood, these data suggest that a mechanical negative feedback system – whereby increased proliferation would cause increased apical cell density, which would in turn promote basal displacement and progenitor differentiation – could help to ensure the robust control of proliferation and differentiation rates in a growing tissue.
