DEAP · Development of Epithelium Apical Polarity: Does the mechanical cell-cell adhesions play a role?
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-05-01 → 2021-04-30
- EU contribution
- €212,934
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Development of Epithelium Apical Polarity: Does the mechanical cell-cell adhesions play a role?
During development, most organs in the body arise from epithelial tubes. Whilst some tubes arise via the folding of an already polarised epithelial tissue, others arise via de novo polarisation in the centre of a previously unpolarised, solid tissue. De novo polarisation happens, for example, during mammalian epiblast formation when the inner-cell-mass (ICM) cells within embryos establish apical-basal polarity and form the amniotic cavity; as well as during teleost neural tube (NT) development when the neuroepithelium progenitor cells epithelialise and open a central lumen. How polarity is initiated in the precisely correct location within these epithelial tubes is therefore a fundamental question in organ development and has great implications in understanding diseases and tissue engineering. This project was proposed to understand how de novo polarisation is initiated during epithelial tube formation, by using mouse embryonic stem cell (mESC) culture, zebrafish models, optogenetics and live cell imaging. Specifically, the project was designed to address the following scientific questions: 1). Whether de novo polarization of epithelial organs is dependent on cell-cell adhesions. 2). Whether polarity establishment depends on cell-cell adhesion-based force. Due to career development, I am ending this fellowship 12 months earlier than the initial proposal. Most of the work proposed till this 12-month time point in the initial proposal have been achieved. No publications have been achieved till the end of period, but I am continuing work in the host laboratory and institution on the project and expecting to publish the results from the project in the next 12-18 months.
Data: CORDIS, © European Union
Project objective
One fundamental question in biology is how are epithelial tubes polarised from initially unpolarised cells to establish coherent tissues. In this project, I will determine the role of cell-cell adhesion mediated force during de novo polarisation of epithelial tubes. I will use two models for the studies of this project. First, I will use a mouse embryo stem cell (mESC) culture model that phenocopies the morphogenesis of the very early mammalian embryo during implantation, when the epiblast forms a centrally located, polarised lumen. This minimal model will allow me to control cell number and cell-cell interaction so that I can analyse the initiation of absolutely naïve junctional adhesions in relation to polarisation. Second, I will use the zebrafish neural tube as an in vivo model of epithelial tube formation. I will use a cutting-edge optogenetic approach to both image and manipulate the process of apicobasal polarisation and junctional formation at the single cell level within a whole vertebrate organ. This will also allow me to compare whether the principles driving polarisation are conserved across different systems. I will carry out this research project under the supervision of Clare Buckley at University of Cambridge. During this project, I will have a perfect chance to apply my knowledge in epithelium cell biology into the studies of vertebrate development, and benefit from expertise across disciplines to establish my network and research filed for my future career. The studies of this project will extend our understanding of the biological importance of cell adhesions and advance our knowledge of the fundamental principles of tissue patterning during development. A better understanding of polarisation during development may help us to understand dysregulation of cell polarity in diseases.
Original text from CORDIS.
Participants
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union