NeuroForceSensor · Does inter-tissue mechanical coupling coordinate neural tube closure?
Horizon Europe — Marie Skłodowska-Curie Actions
- Duration
- 2022-11-01 → 2024-10-31
- EU contribution
- €179,438
- Participants
- 1
- Scheme
- HORIZON-TMA-MSCA-PF-EF
Lines connect the coordinator with its partners.
Results in brief
Does inter-tissue mechanical coupling coordinate neural tube closure?
Neural tube defects (NTDs) are severe congenital malformations of the brain and spine, affecting 1 in 1000 births in Europe. They result from failure of the embryonic neural tube to close, leading to lifelong disabilities. While the cellular and molecular mechanisms are well-studied, the mechanical aspects of neural tube closure are less understood. The project aims to provide a unified biomechanical understanding of neural tube morphogenesis using advanced bioengineering techniques such as intravital 3D bioprinting. This technique enables the construction of force sensors directly inside the neural tube of chicken embryos, which bear striking similarities to the human embryo in early development. The first objective is to map tissue-level mechanical forces during neural tube closure. This will provide an overview of how forces and mechanical properties change over time and between different anatomical locations in the embryo. The second objective is to investigate whether connected epithelia are mechanically coupled, using precise physical perturbations and microfluidic delivery of pharmacological inhibitors. Together, these studies will pave the way for the identification of novel preventive and therapeutic strategies to enhance cellular force-generating mechanisms during neural tube closure. In parallel to data acquisition, the MSCA fellowship aims to foster the development of the individual researcher and provide interdisciplinary training and transferable skills.
Data: CORDIS, © European Union
Project objective
Failure of neural tube closure causes neural tube defects (NTDs), which continue to affect 1:1,000 births in Europe. Successful closure requires poorly understood coordination of cellular force-generating mechanisms in different embryonic tissues. By adopting a novel bio-engineering approach, I aim to generate the first spatiotemporal map of mechanical forces in neural tube closure. This unified biomechanical understanding of morphogenesis will provide a step-change in our interpretation of genetic/teratogenic insults underlying NTDs.In this project, I will identify the physical forces mediating neural tube closure and describe their inter-tissue coordination during development. This will be based on intravital 3D (i3D) bioprinting, a novel method established by the Elvassore group at UniPd (host). This method allows 3D printing of biocompatible force sensors directly inside the neural tube of living chick embryos, a well-established vertebrate model. Combined with cutting edge chemical engineering and computational modelling, I will investigate the spatiotemporal coordination of mechanical forces and assess whether connected epithelial tissues are mechanically coupled. The high positional accuracy of i3D enables previously unfeasible perturbations of morphogenesis to test mechanical coupling between connected epithelia. These physical interventions will be paralleled by microfluidic regional delivery of pharmacological inhibitors to biochemically perturb the same morphogenetic processes. Together these studies will pave the way for the identification of novel preventative and therapeutic strategies to enhance cellular force-generating mechanisms during neural tube closure.
Original text from CORDIS.
Participants
- UNIVERSITA DEGLI STUDI DI PADOVA · PadovaCoordinatorItaly
Links
- View on CORDIS
- DOI: 10.3030/101067028
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e50d8ec555&appId=PPGMS
- https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5170dca67&appId=PPGMS
Data: CORDIS, © European Union