Abstract
Much of our current knowledge of cell polarisation is based on single cells or cultured cellular aggregates in a stable environment, which does not fully recapitulate the complex dynamics of embryonic development. This thesis uses the developing brain of the transparent zebrafish embryo as a model in which to examine polarisation strategies during morphogenesis in vivo. Zebrafish neurulation involves the transformation of an initially solid primordium into an epithelial tube. Prior to this, neural progenitor cells must acquire apico-basal polarity through assembly of apical complexes at the tissue midline.It has been previously shown that a specialised mirror-symmetric cell division, termed C-division, is a major mechanism for apico-basal polarisation. I show that before this division occurs, cells localise apical polarity proteins to the region where they intersect the tissue midline, suggesting that the initial establishment of apico-basal polarity occurs independently of this cell division. I have subsequently investigated the mechanisms by which neural cells are able to sense the tissue architecture and form a lumen at the midline.
During formation of the neural rod, cells from each side interdigitate across the tissue midline. I present evidence that nascent cell-cell contacts in this region add spatial precision to the localisation of apical complexes. In the absence of left-right interactions apical proteins assemble at the anti-basal extremity of the cell, rather than partway along its length. I have additionally examined embryos lacking functional basal lamina components and show that laminin is required for the correct orientation of apico-basal polarity and location of divisions throughout neural tube development.
In conclusion, I show that cells polarise in the interdigitation zone prior division and that a basal cue from the surrounding environment works in concert with cellular interactions across the neural midline to direct the correct spatial assembly of apical junctions and subsequent lumen formation.
| Date of Award | 2014 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Jon Clarke (Supervisor) |