Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.

Autor:	Hansen AH; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Pauler FM; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Riedl M; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Streicher C; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Heger A; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Laukoter S; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Sommer C; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Nicolas A; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Hof B; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Tsai LH; Picower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA., Rülicke T; Department of Biomedical Sciences, University of Veterinary Medicine Vienna, 1210 Vienna, Austria., Hippenmeyer S; Institute of Science and Technology Austria, Am Campus 1, 3400 Klosterneuburg, Austria.
Jazyk:	angličtina
Zdroj:	Oxford open neuroscience [Oxf Open Neurosci] 2022 Jul 07; Vol. 1, pp. kvac009. Date of Electronic Publication: 2022 Jul 07 (Print Publication: 2022).
DOI:	10.1093/oons/kvac009
Abstrakt:	The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general. Competing Interests: All authors declare that they have no conflicts of interest. (© The Author(s) 2022. Published by Oxford University Press.)
Databáze:	MEDLINE
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