Project Reference: TRG27-PDN-CN1

Project title: Investigating how cell and tissue shape affect nuclear arrangements and positioning in pseudostratified epithelia

Project outline

Epithelia are cell sheets that form most organs of the developing embryo.

A particular type of epithelia, pseudostratified epithelia (PSE), are precursors of diverse organs including the central nervous system. Cells in PSE are highly elongated with each cell spanning the full thickness of the sheet. Nuclei can be positioned along the whole cell length. All PSE nuclei have to move to the apical surface for division. This apical movement is essential for tissue integrity and maturation. In PSE of different heights, different mechanisms drive the nucleus apically, ranging from actin polymerisation and actomyosin contractility to motor-based microtubule-dependent transport. So far, it is unclear how exactly tissue and cell shape and height influence mechanisms driving nuclear movement. This is what we will ask in this project. Further, we will explore how the nucleus senses its position and instructs the cytoskeleton to move apically. We will use zebrafish retinal and hindbrain neuroepithelia of similar height but different shape, hemispheric versus cuboidal (Norden Lab). In parallel, we will use cultured epithelial sheets of different heights, grown from epithelial cell lines (MDCK and iPSCs) on gels of varying stiffness (Paluch lab).Alongside measurements and perturbations, cell and tissue shape will be analysed in morphospace to probe how shape influences nuclear arrangements and migration modes. Targeted shape changes of cultured 3D epithelia will then test which boundary conditions influence these parameters. Modelling will be done in collaboration with Guillaume Salbreux (Geneva). 

Project impact: Nuclear arrangements and movements before division are at the core of PSE biology. Understanding the role of tissue and cell shape will set the stage for how PSE build into functional organs. As many 3D culture models, including brain and other organoids, derive from PSE, this project can inform how to grow better-organised 3D tissues as improved disease models.

Principal Supervisor

Professor Caren Norden

Email address: cn288@cam.ac.uk

Department / Partner Institute: Physiology, Development and Neuroscience (PDN)

Website: https://www.gurdon.cam.ac.uk/people/caren-norden/

BBSRC strategic theme

Understanding the rules of life