Glycine receptors control the generation of projection neurons in the developing cerebral cortex

A Avila; P M Vidal; S Tielens; G Morelli; S Laguesse; Robert J Harvey; J M Rigo; L Nguyen

doi:10.1038/cdd.2014.75

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Glycine receptors control the generation of projection neurons in the developing cerebral cortex

Journal article

Peer reviewed

Glycine receptors control the generation of projection neurons in the developing cerebral cortex

A Avila, P M Vidal, S Tielens, G Morelli, S Laguesse, Robert J Harvey, J M Rigo and L Nguyen

Cell Death & Differentiation, Vol.21(11), pp.1696-1708

2014

DOI: https://doi.org/10.1038/cdd.2014.75

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Abstract

Biological Sciences

Medical and Health Sciences

The development of the cerebral cortex requires coordinated regulation of proliferation, specification, migration and differentiation of cortical progenitors into functionally integrated neurons. The completion of the neurogenic program requires a dynamic interplay between cell intrinsic regulators and extrinsic cues, such as growth factor and neurotransmitters. We previously demonstrated a role for extrasynaptic glycine receptors (GlyRs) containing the α2 subunit in cerebral cortical neurogenesis, revealing that endogenous GlyR activation promotes interneuron migration in the developing cortical wall. The proliferative compartment of the cortex comprises apical progenitors that give birth to neurons directly or indirectly through the generation of basal progenitors, which serve as amplification step to generate the bulk of cortical neurons. The present work shows that genetic inactivation of Glra2, the gene coding the α2 subunit of GlyRs, disrupts dorsal cortical progenitor homeostasis with an impaired capability of apical progenitors to generate basal progenitors. This defect results in an overall reduction of projection neurons that settle in upper or deep layers of the cerebral cortex. Overall, the depletion of cortical neurons observed in Glra2-knockout embryos leads to moderate microcephaly in newborn Glra2-knockout mice. Taken together, our findings support a contribution of GlyR α2 to early processes in cerebral cortical neurogenesis that are required later for the proper development of cortical circuits.

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Title: Glycine receptors control the generation of projection neurons in the developing cerebral cortex
Authors: A Avila (Author) - Hasselt University, Germany
P M Vidal (Author) - Hasselt University, Germany
S Tielens (Author) - University of Liège, Belgium
G Morelli (Author) - Hasselt University, Germany
S Laguesse (Author) - University of Liège, Belgium
Robert J Harvey (Author) - University College London, United Kingdom
J M Rigo (Author) - Hasselt University, Germany
L Nguyen (Author) - University of Liège, Belgium
Publication details: Cell Death & Differentiation, Vol.21(11), pp.1696-1708
Publisher: Nature Publishing Group
Date published: 2014
DOI: 10.1038/cdd.2014.75
ISSN: 1350-9047
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99451179302621
Output Type: Journal article

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Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology

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