Award details

Membrane traffic and morphogenesis of the neural tube

Reference	BB/H00260X/1
Principal Investigator / Supervisor	Professor Jonathan Clarke
Co-Investigators / Co-Supervisors
Institution	King's College London
Department	MRC Ctr for Developmental Neurobiology
Funding type	Research
Value (£)	391,944
Status	Completed
Type	Research Grant
Start date	19/10/2009
End date	18/10/2012
Duration	36 months

Abstract

The generation of tissue shape and form is of fundamental importance to embryogenesis and severe and distressing human foetal deformities arise when these processes are disrupted. Examples of this are neural tube defects such as spina bifida and anencephaly that occur when shaping of the neural tube is incomplete. Understanding the mechanisms that shape embryonic tissues may therefore in the long term have significant medical relevance. This proposal investigates neural tube formation in the relatively simple vertebrate, the zebrafish, and is based on a novel mechanism that can orchestrate neural tube development that was recently published in Nature (Tawk et al 2007). The development of tissue shape and structure is one of the least understood aspects of developmental biology. The Tawk et al 2007 paper uncovered a novel role for orientated cell division in initiation of epithelial polarity and lumen formation in the zebrafish neural tube. This proposal will take this observation forward to investigate what the precise mechanism is that links cell division to the generation of a lumen. Other works suggest membrane traffic is involved in completion of cytokinesis and also epithelial polarization, and this raises the interesting hypothesis that, in the fish neural primordium, intracellular membrane traffic simultaneously generates both new membrane to complete cytokinesis and specifies this new membrane and associated molecular complexes as apical in character to initiate cell polarization and lumen formation. We will test this hypothesis by taking advantage of the transparency of the fish embryo for live imaging of lumen formation together with a range of manipulations that will assess the role of intracellular membrane traffic. This work will lead to a significant addition to our understanding of the roles of cell division other than just in growth and renewal.

Summary

During early development embryos generate many organs whose functions are based on a tubular structure, for example blood vessels, kidneys, airways and the brain and spinal cord. Our understanding of the cellular and molecular mechanisms that generate tubular structures are quite limited and most of the best understanding comes from experiments done on cells and tissues grown in culture rather than in the embryos themselves. We propose to study the development of the tubular structure of the brain and spinal cord in zebrafish embryos as this is a system that allows us to both watch via time-lapse microscopy this process in completely intact embryos and manipulate the process by relatively easy experimental methods. We will particularly analyse the way that cell division plays in this process as we have previously shown that a very specialized cell division plays a powerful role in this process. The molecular details of how cell division can generate a tubular structure will be the focus of our work. This work is interesting because the generation of tissue shape and form (in our case a tubular structure) is of fundamental importance to embryogenesis and severe and distressing human foetal deformities arise when these processes are disrupted.

Committee	Research Committee D (Molecules, cells and industrial biotechnology)
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

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