Neurulation: coordinating cell polarisation and lumen formation.

Cell polarisation in development is a common and fundamental process underlying embryo patterning and morphogenesis, and has been extensively studied over the past years. Our current knowledge of cell polarisation in development is predominantly based on studies that have analysed polarisation of single cells, such as eggs, or cellular aggregates with a stable polarising interface, such as cultured epithelial cells (St Johnston and Ahringer, 2010). However, in embryonic development, particularly of vertebrates, cell polarisation processes often encompass large numbers of cells that are placed within moving and proliferating tissues, and undergo mesenchymal-to-epithelial transitions with a highly complex spatiotemporal choreography. How such intricate cell polarisation processes in embryonic development are achieved has only started to be analysed. By using live imaging of neurulation in the transparent zebrafish embryo, Buckley et al (2013) now describe a novel polarisation strategy by which cells assemble an apical domain in the part of their cell body that intersects with the midline of the forming neural rod. This mechanism, along with the previously described mirror-symmetric divisions (Tawk et al, 2007), is thought to trigger formation of both neural rod midline and lumen. Brain morphogenesis in zebrafish is initiated by the convergence movements of yet apicobasally unpolarised neural progenitors towards the dorsal side of the embryo, where they accumulate along the forming body axis giving rise to the neural rod. It is only after the formation of the neural rod, that the neurocoel is formed by cavitation (Papan and Campos-Ortega, 1994). A prerequisite for lumen opening is the formation of a continuous apical surface at the neural rod midline that is free of midline-crossing cell bodies and cellular protrusions (Figure 1). Previous work has suggested that apical midline formation and clearance is achieved by a mode of polarised cell division that gives rise to two mirrorsymmetric daughter cells placed on both sides of the neural rod midline. Since these divisions allow cells to cross the midline, they have also been named crossing divisions (c-division). C-divisions not only distribute cells over the midline but also contribute to cell polarisation by accumulating the apical marker Pard3 at their abscission site (Geldmacher-Voss et al, 2003; Tawk et al, 2007). An instructive function of c-divisions in neural rod midline formation is supported by experiments showing that ectopic c-divisions within the neural rod give rise to ectopic apical midline structures (Tawk et al, 2007; Quesada-Hernández et al, 2010; Zigman et al, 2011) (Figure 1). Yet, in embryos where the c-divisions are inhibited, neural rod midline formation and lumen opening still occur (Ciruna et al, 2006; Tawk et al, 2007; Quesada-Hernández et al, 2010; Zigman et al, 2011) (Figure 1). To understand how the neural rod midline forms in the absence of c-divisions, Buckley et al (2013) have now used mosaic labelling of Pard3 to follow the apicobasal polarisation of neural rod cells in embryos where c-divisions are inhibited. They found that in progenitor cells that cross the neural rod midline region, Pard3 accumulates in the region of the cell that intersects with the position of the future midline. Similar accumulations were also observed in progenitor cells of normal embryos undergoing c-divisions before they enter into mitosis. With cell division progressing in those cells, the Pard3 accumulation domain then localises to the emerging cleavage plane. Together, these observations suggest that neural progenitors initiate apicobasal polarisation before and independently of division (Figure 1). The authors also show that along with the accumulation of Pard3 in the midline-intersecting region of progenitor cells, two more apical structures—the centrosome and Rab11-positive intracellular compartments—also localise to this region. Accumulation of Pard3 and Rab11 at the midline is prevented by depolymerisation of microtubules. Moreover, tissue-specific expression of a dominant-negative Rab11 impaired lumen opening while leaving midline polarisation unaffected, suggesting a novel role for Rab11 in lumen opening independently of cell polarisation. In progenitors crossing the neural rod midline, the microtubule organising centre (MTOC) is initially located centrally at the midline-intersecting region of the cell and organises a mirror-symmetric microtubule network on both sides of the midline. In cases where midlinecrossing cells are not undergoing c-division, one side of the microtubule network reorganises and the cell protrusion associated with this network shrinks progressively until the cell is restricted to one side of the forming midline only. Taken together, these observations suggest that neural progenitors are able to sense the midline. This is the region of the neural rod where the converging progenitor cells from both sides of the neural plate meet and interdigitate. To The EMBO Journal (2013) 32, 1–3 www.embojournal.org