Girdler, G.C.; (2010) Investigating the mechanisms that regulate the establishment of polarity during zebrafish neural tube formation. Doctoral thesis , UCL (University College London).

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Abstract

The establishment of apico-basal polarity and lumen formation are fundamental steps during vertebrate neural tube development. In zebrafish embryos, the lumen is generated de novo from a solid rod structure. Prior to this, the neural cells acquire apico-basal polarity when they undergo mirror-symmetric division and one daughter cell crosses the midline (C‐division). This specialised division must be tightly regulated in time and space for correct neural tube morphogenesis. I have shown that delaying convergence in wildtype tissue results in C‐divisions occurring at the right time but in the wrong place and the generation of neural tube duplications. This uncoupling of individual cell behaviours from tissue morphogenesis suggests that an intrinsic timer controls cell polarisation and Cdivision during neurulation. I have tested this hypothesis by heterochronic cell transplantation. I have found that both younger and older transplanted cells polarise according to their age, show a decreased ability to cross the midline during neurulation, and that older cells can generate ectopic lumens within the host neuroepithelium. These results all support the idea that an intrinsic timer controls cell polarisation and lumen formation. They suggest that the timer begins even before cells are specified as neural, and can resist many environmental signals during gastrulation and neurulation that could reset it. I have also investigated the role of the environment in neural cell polarisation by examining the establishment of polarity of cells in embryos with abnormal neural tube morphogenesis, and in extreme ectopic locations both in the embryo and in 3D culture. Cells can polarise in all these environments, although polarisation can be delayed by 1hour by severe morphogenetic defects. Lastly I have found that cells do not monitor time by counting the number of cell cycles and that cell polarisation does not even require mirror-symmetric cell division. Overall my results highlight the importance of mechanisms that coordinate cell intrinsic programmes with morphogenetic movements and environmental signals, both in time and space, for correct embryogenesis.

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