Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells Journal Article


Author(s): Beattie, Robert; Postiglione, Maria P; Burnett, Laura E; Laukoter, Susanne; Streicher, Carmen; Pauler, Florian M; Xiao, Guanxi; Klezovitch Olga; Vasioukhin, Valeri; Ghashghaei, Troy H; Hippenmeyer, Simon
Article Title: Mosaic Analysis with Double Markers Reveals Distinct Sequential Functions of Lgl1 in Neural Stem Cells
Affiliation IST Austria
Abstract: The concerted production of neurons and glia by neural stem cells (NSCs) is essential for neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) generate nearly all neocortical neurons and certain glia lineages. RGP proliferation behavior shows a high degree of non-stochasticity, thus a deterministic characteristic of neuron and glia production. However, the cellular and molecular mechanisms controlling RGP behavior and proliferation dynamics in neurogenesis and glia generation remain unknown. By using mosaic analysis with double markers (MADM)-based genetic paradigms enabling the sparse and global knockout with unprecedented single-cell resolution, we identified Lgl1 as a critical regulatory component. We uncover Lgl1-dependent tissue-wide community effects required for embryonic cortical neurogenesis and novel cell-autonomous Lgl1 functions controlling RGP-mediated glia genesis and postnatal NSC behavior. These results suggest that NSC-mediated neuron and glia production is tightly regulated through the concerted interplay of sequential Lgl1-dependent global and cell intrinsic mechanisms.
Keywords: EGFR; Neurogenesis; Neural Stem Cells; MADM; lineage; gliogenesis; LGL1; mosaic analysis with double marker; radial glia progenitor; RGP
Journal Title: Neuron
Volume: 94
Issue 3
ISSN: 0896-6273
Publisher: Elsevier  
Date Published: 2017-05-03
Start Page: 517
End Page: 533
DOI: 10.1016/j.neuron.2017.04.012
Notes: We thank Drs. N. Sans and M. Montcouquiol for transferring Lgl1-flox mice and Dr. Threadgill for providing Egfr-flox mice; A. Heger (Preclinical Facility) and E. Papusheva (Bioimaging Facility) for technical support; C. Schwayer, E. Fisher, P. Hirschfeld, M. Frank, and J. Rodarte for initial experiments and/or assistance; J. Knoblich, M. Loose, C.P. Heisenberg, and members of the Hippenmeyer lab for discussion; and A. Kicheva, C. Mieck, N. Amberg, and C. Duellberg for comments on the manuscript. This work was supported by IST Austria institutional funds, NĂ– Forschung & Bildung n[f+b] (C13-002), the European Union (FP7-CIG618444), and a program grant from the Human Frontiers Science Program (RGP0053/2014) to S.H.
Open access: no