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Title: Glycine receptors control the generation of projection neurons in the developing cerebral cortex
Authors: AVILA MACAYA, Ariel 
Vidal, Pia M. 
Tielens, S.
MORELLI, Giovanni 
Laguesse, S.
Harvey, R. J.
Rigo, J. M. 
Nguyen, L.
Issue Date: 2014
Source: CELL DEATH AND DIFFERENTIATION, 21 (11), p. 1696-1708
Abstract: 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 alpha 2 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 alpha 2 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 alpha 2 to early processes in cerebral cortical neurogenesis that are required later for the proper development of cortical circuits.
Notes: [Avila, A.; Vidal, P. M.; Morelli, G.; Rigo, J-M] Hasselt Univ, Biomed Res Inst, Diepenbeek, Belgium. [Avila, A.; Tielens, S.; Morelli, G.; Laguesse, S.; Nguyen, L.] Univ Liege, CHU Sart Tilman, GIGA Neurosci, Liege, Belgium. [Avila, A.; Tielens, S.; Morelli, G.; Laguesse, S.; Nguyen, L.] Univ Liege, CHU Sart Tilman, Interdisciplinary Cluster Appl Genoprote GIGA R, Liege, Belgium. [Nguyen, L.] Univ Liege, CHU Sart Tilman, Walloon Excellence Lifesci & Biotechnol WELBIO, Liege, Belgium. [Harvey, R. J.] UCL Sch Pharm, Dept Pharmacol, London, England.
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ISSN: 1350-9047
e-ISSN: 1476-5403
DOI: 10.1038/cdd.2014.75
ISI #: 000343296800005
Category: A1
Type: Journal Contribution
Validations: ecoom 2015
Appears in Collections:Research publications

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