Previous and ongoing research:

• Projects that tackled optic cup formation, the developmental stage at which the eye acquires its hemispheric shape, revealed that rim cell migration is an essential driver of tissue rearrangements. We exposed the mechanisms by which rim cells move and showed that their interaction with the underlying extracellular matrix is essential for successful cup formation. We further demonstrated that rim cell migration is driven by cryptic lamellipodia that interact with this matrix (Sidhaye and Norden 2017; Soans et al., 2022). Current studies include dissecting the interplay and hierarchies between the three different epithelial rearrangements: neuroepithelial invagination, retinal pigment epithelial flattening and rim migration. To make analysis efficient and reproducible, from cells to tissue we use a combination of opens source software like LimeSeq, StarDist and Ilastic and commercial packages like IMARIS.

• Once the optic cup is formed it features a pseudostratified neuroepithelium hosting proliferating progenitor cells that will differentiate into all retinal neurons at later developmental stages. An important phenomenon that links nuclear and tissue biology during this proliferative stage is interkinetic nuclear migration (IKNM). IKNM ensures that all cell divisions occur at apical positions. We revealed that this apical positioning is crucial to maintain tissue integrity (Strzyz et al., 2015). We further identified the cytoskeletal mechanisms that drive nuclei apically during IKNM and demonstrated that tissue architecture can influence the molecular pathways responsible for moving nuclei to their apical positions before mitosis (Yanakieva et al., 2019). In more recent work, we discovered that also nuclear properties themselves, particularly nuclear stiffness, can influence efficient apical nuclear migration. Furthermore, we show that pseudostratification and nuclear packing play a major role in tissue maturation and tissue shape maintenance.

• When investigating retinal neurogenesis and lamination, we probe the cell biological mechanisms and cell-tissue interplay that underlie retinal patterning. Neuronal migration in the retina is much more complex than, for example, in the well-studied neocortex. As in other parts of the brain, neurons in the retina are often born away from their final functional location and must move to the correct position to form meaningful neuronal networks. We investigate the mechanisms that drive cell migration in the retina. Many of the emerging retinal neurons, including retinal ganglion cells, photoreceptors and amacrine cells, undergo an initial phase of somal translocation, a phenomenon also prominently observed in other parts of the brain (Icha et al., 2016) (Rocha-Martins et al., 2023). In addition to this more canonical form of neuronal translocation, horizontal cells use ameboid-like migration to find their final target area (Amini et al., 2019; Amini et al., 2022). We currently aim to understand what parameters differentiate one migration mode from the other and how this coordinates growth and lamination that occur simultaneously (Rocha-Martins et al., 2023).

• In a more recent line of work, we started investigating aspects that ensure bilateral eye formation. While symmetric eye formation is required for optimal visual function not much is known about the naturally occurring variability during eye formation. We also have no appreciation of the system’s capacity for compensation to counteract deviations and the underlying mechanisms that could guide compensation. We thus investigate the signalling cascades and extent of eye-to-eye and eye-to-brain communications involved in bilateral eye formation. We explore bilaterality of two critical stages, optic cup formation and neurogenesis onset and propagation, making use of our vast knowledge of cell and tissue biology involved in these morphogenesis events.

Possible future projects in the lab include but are not limited to:

• Investigating retinal growth and the switch to differentiation.
• Probing cell and tissue biology of retinal lamination.
• Exploring the influence of temperature on reproducible eye formation from optic cup to neurogenesis.
• Examining bilaterality of optic cup formation: Naturally occurring variation and the systems response to induced asymmetry.
• Studying neurogenesis onset and propagation within and across eyes: Influence of inter-organ communication.
• Extracting the influence of bilaterality cues on reproducible retinal organoid formation.
• ….

We are open to all things ‘retina’ that help us understand how the bilateral eyes emerge from cells to tissue, from optic cup to neurogenesis and from zebrafish to human organoids.

Rocha-Martins M, Kretzschmar J, Nerli E, Weigert M, Icha J, Myers EW, Norden C (2023) Bidirectional neuronal migration coordinates retinal morphogenesis by preventing spatial competition. Nature. doi: 10.1038/s41586-023-06392-y

Nerli E, Kretzschmar J, Bianucci T, Rocha-Martins M, Zechner C, Norden C# (2023) Title not provided. EMBO J. doi: 10.15252/embj.2022112657

Soans KG, Ramos AP, Sidhaye J, Krishna A, Solomatina A, Hoffmann KB, Schlüßler R, Guck J, Sbalzarini IF, Modes CD, Norden C# (2022) Collective cell migration during optic cup formation features changing cell-matrix interactions linked to matrix topology. Curr Biol. doi: 10.1016/j.cub.2022.09.034

Amini R, Bhatnagar A, Schlüßler R, Möllmert S, Guck J, Norden C (2022) Amoeboid-like migration ensures correct horizontal cell layer formation in the developing vertebrate retina. eLife. doi: 10.7554/eLife.76408

Nerli E, Rocha-Martins M#, Norden C (2020) Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway. eLife. doi: 10.7554/eLife.60462

Yanakieva I, Erzberger A, Matejcic M, Modes CD, Norden C (2019) Tissue shape determines actin-dependent nuclear migration mechanisms in neuroepithelia. J Cell Biol. doi:10.1083/jcb.201901077

Matejcic M, Salbreux G, Norden C (2018) A non-cell-autonomous actin redistribution enables isotropic retinal growth. PLoS Biol. 16(8). doi: 10.1371/journal.pbio.2006018

Sidhaye J, Norden C (2017) Concerted action of neuroepithelial basal shrinkage and active epithelial migration ensures efficient optic cup morphogenesis. eLife. doi: 10.7554/eLife.22689

Icha J, Kunath C, Rocha-Martins M, Norden C (2016) Independent modes of ganglion cell translocation guide correct lamination in the zebrafish retina. J Cell Biol. 215(2). doi: 10.1083/jcb.201604095

Strzyz PJ, Lee HO, Sidhaye J, Weber IP, Leung LC, Norden C (2015) Interkinetic nuclear migration is centrosome independent and ensures apical cell division to maintain tissue integrity. Dev Cell. doi: 10.1016/j.devcel.2014.12.001

2020 EMBO member

2015 – 2018 EMBO Young Investigator Program (YIP)

2015 José A. Campos-Ortega Young Scientist Award, German Society for Developmental Biology

2012 – 2016 HFSP Career Development Award

2007 – 2010 HFSP Long Term Fellowship Award

Interview with Caren Norden

Current:

• ERC: European Research Council
• FCT: Fundação para a Ciência e a Tecnologia (Foundation for Science and Technology, Portugal)

Previous:

• DFG: Deutsche Forschungsgemeinschaft (German Research Foundation)
• HFSP: Human Frontier Science Program
• EMBO: European Molecular Biology Organization