Project Details

 

Type: ERC - Consolidator Grant

Duration: December 1, 2017 - November 30, 2022

Granted money: EUR 1.996.030

Project number: 725780 (LinPro)

 

Abstract

The cerebral cortex consists of an extraordinary number and great diversity of neurons. Yet, how the cortical entity, with all its functional neuronal circuits, arises from the neural stem cells (NSCs) in the developing neuroepithelium is a major unsolved question in Neuroscience. Radial glia progenitors (RGPs) are responsible for producing nearly all neocortical neurons and a certain fraction of cortical glia including astrocytes. Our recent efforts provide evidence for a high degree of non-stochasticity and thus deterministic nature of RGP behavior in the mammalian neocortex. However, the cellular and molecular mechanisms controlling RGP lineage progression through proliferation, neurogenesis and especially gliogenesis are unknown. In a pursuit to obtain definitive insights into these fundamental questions we assess RGP lineage progression at the unprecedented single cell resolution, using the unique genetic MADM (Mosaic Analysis with Double Markers) technology. MADM offers an unparalleled approach to visualize and concomitantly manipulate sparse clones and small subsets of genetically defined neurons.

Within the scope of this project we will use multidisciplinary experimental approaches to establish a research program with the following major objectives: We will 1) Functionally dissect the relative contribution of cell-autonomous intrinsic signaling and cell-non-autonomous effects in RGP lineage progression; 2) Define the principles of lineage progression in human RGPs in situ using MADM technology in cerebral organoid system; 3) Decipher the logic of glia lineage progression in the neocortex. The ultimate goal of the proposed research is to establish a definitive quantitative framework and mechanistic model of lineage progression in cortical NSCs. As such, the proposed research shall precipitate into extensive conceptual progress regarding the fundamental cellular and molecular principles of cerebral cortex development.

 

Current Project Members

 

Simon Hippenmeyer (Professor)

Robert Beattie (Post Doc)

Susanne Laukoter (Post Doc)

Florian Pauler (Technician)

Carmen Streicher (Technician)

 

Publications

 

Susanne Laukoter, Florian Pauler, Robert Beattie, Nicole Amberg, Andi Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, Simon Hippenmeyer, Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex, Neuron (2020) in press

Robert Beattie, Carmen Streicher, Nicole Amberg, Giselle Cheung, Ximena Contreras, Andi H. Hansen, Simon Hippenmeyer, Lineage Tracing and Clonal Analysis in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM), Journal of Visual Experiments 159, e61147 (2020)

Robert Beattie, Simon Hippenmeyer, Florian M. Pauler, SCOPES: Sparking Curiosity Through Open-Source Platforms in Education and Science, Frontiers in Education feduc.2020.00048 (2020)

Susanne Laukoter, Robert Beattie, Florian M. Pauler, Nicole Amberg, Keiichi I. Nakayama, Simon Hippenmeyer, Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex development, Nature communications 11, 195 (2020)

Alfredo Llorca, Gabriele Ciceri, Robert Beattie, Fong Kuan Wong, Giovanni Diana, Eleni Serafeimidou-Pouliou, Marian Fernández-Otero, Carmen Streicher, Sebastian J Arnold, Martin Meyer, Simon Hippenmeyer, Miguel Maravall, Oscar Marin, A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture, eLife 2019;8:e51381 (2019)

Noemi Picco, Simon Hippenmeyer, Julio Rodarte, Carmen Streicher, Zoltán Molnár, Philip K. Maini, Thomas E. Woolley, A mathematical insight into cell labelling experiments for clonal analysis, Journal of Anatomy 235, 3, 687-696 (2019)

L. Telley, G. Agirman, J. Prados, N. Amberg, S. Fièvre, P. Oberst, G. Bartolini, I. Vitali, C. Cadilhac, S. Hippenmeyer, L. Nguyen, A. Dayer, D. Jabaudon, Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex, Science 364, 6440 (2019)

Gonzalo Ortiz-Álvarez, Marie Daclin, Asm Shihavuddin, Pauline Lansade, Aurélien Fortoul, Marion Faucourt, Solène Clavreul, Maria-Eleni Lalioti, Stavros Taraviras, Simon Hippenmeyer, Jean Livet, Alice Meunier, Auguste Genovesio, Nathalie Spassky, Adult Neural Stem Cells and Multiciliated Ependymal Cells Share a Common Lineage Regulated by the Geminin Family Members, Neuron 102, 1, 159-172 (2019)

Nicole Amberg, Susanne Laukoter, Simon Hippenmeyer, Epigenetic cues modulating the generation of cell‐type diversity in the cerebral cortex, Journal of Neurochemistry 149, 1, 12-26 (2018)

  

Preprints

 

Tingting Zhang, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand, Ximena Contreras, Andi H. Hansen, Carmen Streicher, Marica Anderle, Luca Tiberi, Simon Hippenmeyer, Bassem A. Hassan, Generation of neuronal diversity from common progenitors via Notch signaling in the cerebellum, bioRxiv 10.1101/2020.03.18.997205 (2020)

Ximena Contreras, Amarbayasgalan Davaatseren, Nicole Amberg, Andi. H. Hansen, Johanna Sonntag, Lill Andersen, Tina Bernthaler, Anna Heger, Randy Johnson, Lindsay A. Schwarz, Liqun Luo, Thomas Rülicke, Simon Hippenmeyer, A Genome-wide Library of MADM Mice for Single-Cell Genetic Mosaic Analysis, bioRxiv 10.1101/2020.06.05.136192 (2020)

Yukari H. Takeo, Andrew S. Shuster, Linnie Jiang, Miley Hu, David J. Luginbuhl, Thomas Rülicke, Ximena Contreras, Simon Hippenmeyer, Mark J. Wagner, Surya Ganguli, Liqun Luo, GluD2- and Cbln1-mediated Competitive Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells, bioRxiv 10.1101/2020.06.14.151258 (2020)

Alfredo Llorca, Gabriele Ciceri, Robert Beattie, Fong K. Wong, Giovanni Diana, Eleni Serafeimidou, Marian Fernández-Otero, Carmen Streicher, Sebastian J. Arnold, Martin Meyer, Simon Hippenmeyer, Miguel Maravall, Oscar Marín, Heterogeneous progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture, bioRxiv 10.1101/494088 (2018) published eLife

 

 

Former Project Members

 

Nicole Amberg (Post Doc)

Ximena Contreras (PhD Student)

Amarbayasgalan Davaatseren (Technician)