Ruhr-Universität Bochum

Neuroanatomie und Molekulare Hirnforschung

Prof. Dr. rer. nat. Eckart Förster


Ruhr-Universität Bochum
Institut für Anatomie
Abteilung für Neuroanatomie und Molekulare Hirnforschung


Layering and wiring of neurons in the cerebral cortex

During development of the cerebral cortex, postmitotic neurons migrate from the ventricular zone towards the marginal zone and form the layered structure of the cerebral cortex. Correct positioning and development of cortical neurons is controlled by Reelin, a protein that is expressed and secreted by Cajal Retzius (CR) cells, early generated neurons which are located in the marginal zone of the developing cortex (Förster et al., 2006). Reelin effects on cytoskeletal elements of migrating neurons and on synaptic transmission of adult neurons are mediated by the apolipoprotein E receptor 2 (ApoER2) and the very low density lipoprotein receptor (vldlr), both of which are receptors of the lipoprotein receptor family. Deficiency for Reelin or its receptors leads to severe neuronal migration defects. Reelin deficiency in the developing human cerebral cortex causes lissencephaly, a malformation that is associated with severe mental retardation. It is poorly understood how Reelin modulates neuronal function in the adult brain, where this protein is expressed by interneurons. The objective of our present research is to characterize Reelin dependent functions of neurons in both the developing and the adult brain. We are currently using a conditional Reelin-deficient mouse mutant as a model to study the effects of induced Reelin deficiency at specific time points. In our experiments, we combine histology, molecular biological techniques and cell biological techniques with confocal microscopy as well as live cell imaging of cultured neurons and organotypic slice cultures.

Link to Publications

Selected articles

  • Editorial: Extracellular matrix in development and disorders of the nervous system.
    Jakovcevski I, Andjus PR, Förster E. Front Cell Dev Biol. 2023 Feb 13;11:1153484. doi: 10.3389/fcell.2023.1153484.
  • Weninger J, Meseke M, Rana S, Förster E. Heat-Shock Induces Granule Cell Dispersion and Microgliosis in Hippocampal Slice Cultures. Front Cell Dev Biol. 2021 Feb 22;9:626704. doi: 10.3389/fcell.2021.626704. PMID: 33693000; PMCID: PMC7937632.
  • Jakovčevski I, Förster E, Reiss G, Schachner M. Impact of Depletion of Microglia/Macrophages on Regeneration after Spinal Cord Injury. Neuroscience. 2021 Apr 1;459:129-141. doi: 10.1016/j.neuroscience.2021.02.010. Epub 2021 Feb 13. PMID: 33588005.
  • Hamad MIK, Jbara A, Rabaya O, Petrova P, Daoud S, Melliti N, Meseke M, Lutz D, Petrasch-Parwez E, Schwitalla JC, Mark MD, Herlitze S, Reiss G, Herz J, Förster E. Reelin signaling modulates GABAB receptor function in the neocortex. J Neurochem. 2021 Mar;156(5):589-603. doi: 10.1111/jnc.14990. Epub 2020 Mar 13. PMID: 32083308; PMCID: PMC7442713.
  • Bijelić D, Adžić M, Perić M, Jakovčevski I, Förster E, Schachner M, Andjus PR. Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation. Front Immunol. 2021 Feb 19;11:624612. doi: 10.3389/fimmu.2020.624612. Erratum in: Front Immunol. 2021 Mar 16;12:672476. PMID: 33679718; PMCID: PMC7934619.
  • Pinto RM , Arning L, Giordano JV, Razghandi P, Andrew MA, Gillis T, Correia K, Grote Urtubey D-M, Parwez CR, Hein S, Nguyen HP, Förster E, Beller Jayadaev S, Keene CD Thomas D. Bird TD, Lucente D, Vonsattel J-P, Orr H, Saft C, Petrasch-Parwez E, Wheeler VC (2020). Patterns of CAG repeat instability in the central nervous system and periphery in Huntington’s disease and in spinocerebellar ataxia type 1. Hum. Mol. Genet.,
  • Hamad MIK, Daoud S, Petrova P, Rabaya O, Jbara A, Melliti N, Stichmann S, Reiss G, Herz J, Förster E. (2020) Biolistic transfection and expression analysis of acute cortical slices. J Neurosci Methods. doi: 10.1016/j.jneumeth.2020.108666.
  • Wang S, Li X, Zhang Q, Chai X, Wang Y, Förster E, Zhu X, Zhao S. Cereb Cortex. (2020) Nyap1 regulates multipolar-bipolar transition and morphology of migrating neurons by Fyn phosphorylation during corticogenesis- Cerebral Cortex 30, 929-941. doi: 10.1093/cercor/bhz137.
  • Lutz D, von Düring M, Corvace F, Augustinowski L, Trampe A-K, Nowak M, Förster E (2019). Assessment of Ultrastructural Neuroplasticity Parameters After In Utero Transduction of the Developing Mouse Brain and Spinal Cord. J Vis Exp. 144, 10.3791/59084.
  • Schreiber S, Petrasch-Parwez E, Porrmann-Kelterbaum E, Förster E, Epplen JT, Gerding WM. (2018). Neurodegeneration in the olfactory bulb and olfactory deficits in the Ccdc66 -/- mouse model for retinal degeneration. IBRO Rep. 5, 43-53.
  • Cheng X, Li K, Liu M, Xu M, Hu X, Yan R, Förster E, Zhao S (2018). The effect of P85 on neuronal proliferation and differentiation during development of mouse cerebral cortex. Dev Biol. 441, 95-103.
  • Ismail FS, Moinfar Z, Prochnow N, Dambach H, Hinkerohe H, Haase C G, Förster E, Faustmann P M (2017). Dexamethasone and levetiracetam reduce hetero-cellular gap-junctional coupling between F98 glioma cells and glial cells in vitro. J Neurooncol. 131, 469-476.
  • Meseke M, Rosenberger G, Förster E (2013) Reelin and the Cdc42/Rac1 guanine nucleotide exchange factor alphaPIX/Arhgef6 promote dendritic Golgi translocation in hippocampal neurons. Europ J Neurosci. 37, 1404-1412.
  • Meseke M, Cavus E, Förster E (2013) Reelin promotes microtubule dynamics in processes of developing neurons. Histochem Cell Biol. 139, 283-297.
  • Meseke M, Förster E (2013) A 3D-matrigel/microbead assay for the visualization of mechanical tractive forces at the neurite-substrate interface of cultured neurons. J Biomed Mater Res Part A 101 (6),1726–1733.
  • Lindhorst T, Kurz H, Sibbe M, Meseke M, Förster E (2012). Congruence of vascular network remodeling and neuronal dispersion in the hippocampus of reelin-deficient mice. Histochem Cell Biol. 137, 629-639.
  • Sibbe M, Förster E, Basak O, Taylor V, Frotscher M (2009). Reelin and Notch1 cooperate in the development of the dentate gyrus. J Neurosci 29, 8578-8585.
  • Chai X, Förster E, Zhao S, Bock, HH, Frotscher, M (2009). Reelin stabilizes the actin cytoskeleton of neuronal processes by inducing n-cofilin phoshorylation at serine3. J Neurosci 29, 288-299.
  • Müller MC, Osswald M, Tinnes S, Häussler U, Jacobi A, Förster E, Frotscher M, Haas CA (2009). Exogenous reelin prevents granule cell dispersion in experimental epilepsy. Exp Neurol 216, 390-397.
  • Zhao S, Chai X, Förster E, Frotscher M (2004). Reelin is a positional signal for the lamination of dentate gyrus cells. Development 131, 5117-5125.
  • *Zhao S, *Förster E, Chai X, Frotscher M (2003). Different signals control laminar specificity of commissural and entorhinal fibers to the dentate gyrus. J. Neurosci. 23, 7351-7357. (*equally contributed)
  • Hartfuss E, Förster E, Bock HH, Hack MA, Leprince P, Luque JM, Herz J, Frotscher M, Götz M (2003). Reelin signaling to radial glia affects their morphology and biochemical maturation. Development 130, 4587-4596.
  • Frotscher M, Haas C, Förster E (2003). Reelin controls granule cell migration in the dentate gyrus by acting on the radial glial scaffold. Cereb Cortex 13, 634-640.
  • Bock HH, Jossin Y, Liu P, Förster E, May P, Goffinet AM, Herz J (2003). PI3-Kinase interacts with the adaptor protein Dab1 in response to Reelin signaling and is required for normal cortical lamination. J. Biol. Chem. 278, 38772-38779.
  • Arnaud L, Ballif B A, Förster E, Cooper J A (2003). Fyn tyrosine kinase is a critical regulator of Disabled-1 during brain development. Curr Biol 13, 9-17.
  • Weiss K-H, Johanssen C, Tielsch A, Saum B, Frotscher M, Förster E (2003). Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice and ApoER2/VLDLR deficient mice. J Comp Neurol 460, 56-65.
  • Förster E, Tielsch A, Saum B, Weiss K-H, Johanssen C, Graus-Porta D, Müller U, Frotscher M (2002) Reelin, Disabled1, and b1-class integrins are required for the formation of the radial glial scaffold in the hippocampus. Proc Natl Acad Sci 99, 13178-13183.
  • Weeber EJ, Beffert U, Jones C, Christian JM, Förster E, Sweatt JD, Herz J (2002). Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning. J Biol Chem 277, 39944-39952.
  • Förster E, Zhao S, Frotscher M (2001). Hyaluronan-associated adhesive cues control fiber segregation in the hippocampus. Development 128, 3029-3039.
  • Förster E, Kaltschmidt C, Deng J, Cremer H, Deller T, Frotscher M (1998). Lamina-specific cell adhesion on living slices of hippocampus. Development 125, 3399-3410.
  • Förster E, Naumann T, Deller T, Straube A, Nitsch R, Frotscher M (1997). Cholinergic sprouting in the rat fascia dentata after entorhinal lesion is not linked to early changes in neurotrophin messenger RNA expression. Neuroscience 80, 731-739.
  • Del Rio JA, Heimrich B, Borrell V, Förster E, Drakew A, Alcántara S, Nakajima K, Miyata T, Ogawa M, Mikoshiba K, Derer P, Frotscher M, Soriano E (1997). A role for Cajal-Retzius cells and reelin in the development of hippocampal connections. Nature 385, 70-74.
  • Förster E (1994a). An improved general method to generate internal standards for competitive PCR, BioTechniques 16, 18-20.

Review articles

  • Förster E (2014) Reelin, neuronal polarity and process orientation of cortical neurons. Neuroscience 269, 102-111.
  • Förster E, Bock HH, Herz J, Chai X, Frotscher M, Zhao S (2010). Emerging topics in Reelin function. Eur J Neurosci. 31(9),1511-1518.
  • Frotscher M, Zhao S, Förster E (2007). Development of cell and fiber layers in the dentate gyrus. Prog Brain Res 163, 133-42.
  • Förster E, Zhao S, and Frotscher M (2006b). Laminating the hippocampus. Nat Rev Neurosci 7, 259-267.
  • Förster E, Jossin Y, Zhao S, Chai X, Frotscher M, Goffinet A M (2006a). Recent progress in understanding the role of Reelin in radial neuronal migration, with specific emphasis on the dentate gyrus. Eur J Neurosci 23, 901-909.
  • Frotscher M, Zhao S, Förster E (2004). Wie kommt es zur Schichtung im Hippocampus? Neuroforum 1, 151-155.
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