The retina as a model to explore the cell biology of morphogenesis – from pseudostratification to neuronal arrangements
Previous and Current Research
The overall goal of the research in the lab is to understand organ formation from the cellular to the tissue level. We use the zebrafish retina as our main model. Zebrafish is a an outstanding model organism to investigate these questions due to its advantages in live imaging and its improving ease of genetic manipulations.
As one of our main goals we aim to understand how the retina forms evolving from the eyefield into a multilayered neuronal structure. This developmental program starts with the onset of pseudostratification, which means that cells become highly elongated having their nuclei dispersed along the whole apico-basal axis of the epithelium. These pseudostratified neuroepithelia then give rise to all retinal neurons and we want to understand which neurons are born at which location and time in development. Furthermore we aim to elucidate how neurons once born reach their final position at which they polarize and fulfill their function.
To this end we use quantitative live imaging approaches as well as super-resolution methods. To get an even deeper understanding of events we recently also started collaborations with theorists. Overall our research therefore spans a broad range of developmental programs that lead to the formation of highly organized central nervous system structures. We are sure that many findings we make in the retina can be extrapolated to other, less accessible parts of the brain.
Future Projects and Goals
- Understanding pseudostratification: Kinetics, mechanics and subcellular components
- A quantitative analysis of forces and mechanics during Interkinetic Nuclear Migration in a 3D in vivo environment
- Dissecting cell cycle events and their links to cytoskeletal dynamics in retinal progenitor cells
- The role of basal progenitors in retinal development
- Studies of kinetics and mechanics of neuronal migration modes in the retina
Methodological and Technical Expertise
- Imaging (live imaging, SPIM, confocal microscopy, superresolution)
- Quantitative analysis (Fiji, MatLab, R)
- Theoretical approaches
- Molecular biology
Strzyz, Paulina J.; Lee, Hyun O.; Sidhaye, Jaydeep; Weber, Isabell P.; Leung, Louis C.; Norden, Caren
Interkinetic nuclear migration is centrosome independent and ensures apical cell division to maintain tissue integrity.
Developmental Cell (in press)
Weber, Isabell; Ramos, Ana P.; Strzyz, Paulina J.; Leung, Louis; Young, Stephen; Norden, Caren
Mitotic Position and Morphology of Committed Precursor Cells in the Zebrafish Retina Adapt to Architectural Changes upon Tissue Maturation.
Cell Rep., 7, no. 1, pp. 1–12 (2014)
Lee, Hyun O.; Norden, Caren
Mechanisms controlling arrangements and movements of nuclei in pseudostratified epithelia.
Trends Cell Biol., 23, no. 2, pp. 141–150 (2013)
Leung, Louis; Klopper, Abigail; Grill, Stephan W.; Harris, William A; Norden, Caren
Apical migration of nuclei during G2 is a prerequisite for all nuclear motion in zebrafish neuroepithelia.
Development, 138, no. 22, pp. 5003–5013 (2011)
Norden, Caren; Young, Stephen; Link, Brian A; Harris, William A.
Actomyosin is the main driver of interkinetic nuclear migration in the retina.
Cell, 138, no. 6, pp. 1195–1208 (2009)