Caudally pronounced deficiencies in preplate splitting and migration underly a rostro-caudal progression of cortical lamination defects in the reeler brain

In mammalian neocortex development, every cohort of newborn neurons is guided toward the marginal zone, leading to an “inside-out” organization of the 6 neocortical layers. This migratory pattern is regulated by the extracellular glycoprotein Reelin. The reeler mouse shows a homozygous mutation of t...

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Main Authors: Moreno, Nieves Mingo (Author) , Truschow, Pavel (Author) , Staiger, Jochen F. (Author) , Wagener, Jan Robin (Author)
Format: Article (Journal)
Language:English
Published: February 2024
In: Cerebral cortex
Year: 2024, Volume: 34, Issue: 2, Pages: 1-20
ISSN:1460-2199
DOI:10.1093/cercor/bhae023
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1093/cercor/bhae023
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/cercor/article/34/2/bhae023/7611065
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Author Notes:Nieves Mingo-Moreno, Pavel Truschow, Jochen F. Staiger, Robin J. Wagener
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Summary:In mammalian neocortex development, every cohort of newborn neurons is guided toward the marginal zone, leading to an “inside-out” organization of the 6 neocortical layers. This migratory pattern is regulated by the extracellular glycoprotein Reelin. The reeler mouse shows a homozygous mutation of the reelin gene. Using RNA in situ hybridization we could demonstrate that the Reelin-deficient mouse cortex (male and female) displays an increasing lamination defect along the rostro-caudal axis that is characterized by strong cellular intermingling, but roughly reproduces the “inside-out” pattern in rostral cortex, while caudal cortex shows a relative inversion of neuronal positioning (“outside-in”). We found that in development of the reeler cortex, preplate-splitting is also defective with an increasing severity along the rostro-caudal axis. This leads to a misplacement of subplate neurons that are crucial for a switch in migration mode within the cortical plate. Using Flash Tag labeling and nucleoside analog pulse-chasing, we found an according migration defect within the cortical plate, again with a progressive severity along the rostro-caudal axis. Thus, loss of one key player in neocortical development leads to highly area-specific (caudally pronounced) developmental deficiencies that result in multiple roughly opposite rostral versus caudal adult neocortical phenotypes.
Item Description:Gesehen am 14.01.2025
Physical Description:Online Resource
ISSN:1460-2199
DOI:10.1093/cercor/bhae023