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Addressing the impact of surface ectoderm and somitic mesoderm development on neural tube morphogenesis.

Project description

Identifying the forces behind nervous system development

During development, the nervous system emerges from the neural plate, a complex structure that requires the coordination of multiple tissues. The neural plate folds into a neural tube which eventually closes to form the brain and spinal cord. Failure to do so leads to neural tube defects (NTDs). The EU-funded Neural Tube project is interested to study the process of neural tube closure from a mechanical perspective. Using Xenopus laevis and mouse embryos as model systems, researchers aim to investigate the contribution of other tissues to neural tube closure. Project results will offer fundamental information on the origin of human development and NTDs.

Objective

Neural tube closure (NTC) is a fundamental process during vertebrate embryogenesis, which leads to the formation of the central nervous system. Defective NTC leads to neural tube defects (NTDs), which are one of the most common human birth defects. During NTC Convergent Extension (CE) leads to the narrowing and elongation of the neural plate (NP) and Apical Constriction (AC) drives the bending of the tissue. While the role of the aforementioned morphogenetic events for NTC has been studied extensively how the development of tissues mechanically coupled with the NP affects NTC remains poorly understood. Here, we aim to elucidate the influence of surface ectoderm (SE) and somitic mesoderm (SM) morphogenesis on NTC. To achieve our goals, we will employ an interdisciplinary research plan using Xenopus laevis and mouse embryos as model systems. First, to understand the contribution of SE and SM morphogenesis on NTC (AC and CE) we will specifically inhibit these processes using morpholino mediated protein knock-down in Xenopus embryos and tissue-specific knock-out and knock-in models in mice embryos. Subsequently, we will directly assess the impact of SE and SM tissue tension on NTC by modulating tissue tension in Xenopus embryos through optogenetic tools and mutant constructs in conjunction with live imaging. We will go on to examine how SE and SM influence the mechanical landscape of the NP using force inference techniques in Xenopus and mouse embryos in conjunction with loss of function approaches described above. Finally, we will examine how mechanical coupling between the NP with both the SE and SM affects the mechanosensitive elements responsible for CE and AC. Overall the data produced by the proposed work will uncover the role of SE and SM morphogenesis on NTC expanding our understanding of human NTDs, while at the same time providing precious insights with respect to the coordination and coupling of mechanical force generators during embryonic development.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-WF-2018-2020

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Coordinator

UNIVERSITY OF CYPRUS
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 157 941,12
Address
AVENUE PANEPISTIMIOU 2109 AGLANTZI
1678 Nicosia
Cyprus

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Region
Κύπρος Κύπρος Κύπρος
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 157 941,12
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