Award details

Neural tube development

Reference	BB/F002424/2
Principal Investigator / Supervisor	Professor Jonathan Clarke
Co-Investigators / Co-Supervisors
Institution	King's College London
Department	BHS School Management
Funding type	Research
Value (£)	226,007
Status	Completed
Type	Research Grant
Start date	01/08/2008
End date	31/07/2010
Duration	24 months

Abstract

The zebrafish embryo uses a novel specialised mode of cell division to generate the tissue organisation required for neural tube formation. This mode of division we have called mirror-symmetric division because it generates pairs of daughter cells with mirror-image apico-basal polarity. A key event in this division is the polarised distribution of the polarity protein Par3 so that it accumulates at the cleavage furrow, from where it can be mirror-symmetrically inherited in a polarised way in the two daughters. Here we will determine which other proteins contribute to this polarised division to determine the prospective apical and basal domains of the daughter cells. We will also address whether tight junction proteins and adherens junctions proteins play an important role in this division by tethering daughter cell together after division - a registration of daughter cells seems to be important for accurate placement of the prospective apical domain of the neuroepithelium. Finally we will determine whether this novel mechanism of morphogenesis operates in other organ systems such as the gut that also develops a tubular morphology from a solid rod primordium.

Summary

A key early step during development of the brain and spinal cord is the mechanism of neural tube closure. This is the mechanism that transforms the early brain primordium from a flat sheet of cells into a tube. The tubular structure is then maintained through to adulthood. When this embryonic process goes wrong, neural tube defects such as spina bifida result. We have recently discovered that in the zebrafish embryo this process depends on a novel mode of cell division, which we have termed mirror-symmetric division. We will investigate which molecular mechaisms are important in the regulation of this novel mode of cell division. In particular we will concentrate on a proteins whose role in the development of invertebrate embryos strongly suggest they could contribute to the control of mirror-symmetric divisions. We will also investigate how this division generates cells that are bound together in an arrangement that allows the tubular structure to develop. It is uncertain at present whether other vertebrate embryos employ this specialised mode of division in brain development, but there is some reason to believe that frog embryos and chick embryos could use a similar process. In this work we will determine whether mirror-symmetric divisions are present in the early frog and chick embryo neural tubes. In addition we will determine whether other parts of the embryo that also generate tubular structures (like the gut) also use mirror-symmetric division as a step in the generation of tubes.

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

Associated awards:

BB/F002424/1 Neural tube development

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