Award details

Cellular and molecular mechanisms of neurulation

Reference	BB/C516952/1
Principal Investigator / Supervisor	Professor Jonathan Clarke
Co-Investigators / Co-Supervisors	Dr Marcel Tawk
Institution	University College London
Department	Cell and Developmental Biology
Funding type	Research
Value (£)	284,253
Status	Completed
Type	Research Grant
Start date	01/06/2005
End date	31/05/2008
Duration	36 months

Abstract

The aim of this proposal is to analyse at high resolution the morphologies and movements of individual cells during the process of neurulation in a vertebrate embryo in both wildtype and mutant individuals. Neurulation is a critical early step in formation of the central nervous system and of significant clinical relevance because neural tube defects that result from defective neurulation represent the second most common malformations during human pregnancies. We will study neurulation in zebrafish embryos because we believe zebrafish offer a unique opportunity to study the cellular events of neurulation and their molecular control. The transparency of the fish embryo enables us to make high resolution timelapse analyses of cell behaviour during normal neurulation. We will compare this to what is known about cellular events in amphibian, avian and mammalian neurulation in order to understand the common and divergent mechanisms across these species. The process of neurulation in the fish has been surprisingly neglected so it is likely we will generate a lot of novel data. Secondly we will define the role of Planar Cell Polarity pathway in the cellular events of neurulation. The PCP pathway has been shown to be crucial to correct neurulation in both mammals and amphibians, but the exact roles that this pathway plays in this process is not known as high resolution analysis of cell behaviour has not been possible in these animals. We will use mutant and morphant analysis to reveal which components of this pathway control which cell behaviours in the process of neurulation. Thirdly we will assess the role of underlying mesoderm in movements of neurulation. By using a transplantation strategy to target PCP mutant cells to either neurectoderm only or mesoderm only we will be able to dissect the contribution of mesoderm movements to the success of neurulation. We will attempt to determine which phases of neurulation (eg. convergence, epithelial organisation, folding, intercalation, fusion) are autonomous to neural plate and neural keel cells and which are driven wholly or to some degree by the Convergent Extension movements of the underlying mesoderm.

Summary

unavailable

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

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