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Neuregulin-4 is required for maintaining soma size of pyramidal neurons in the motor cortex

Paramo, Blanca, Bachmann, Sven O., Baudouin, Stéphane J., Martinez Garay, Isabel and Davies, Alun M. 2021. Neuregulin-4 is required for maintaining soma size of pyramidal neurons in the motor cortex. eNeuro 8 (1) , 0288-20.2021. 10.1523/ENEURO.0288-20.2021

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Abstract

The regulation of neuronal soma size is essential for appropriate brain circuit function and its dysregulation is associated with several neurodevelopmental disorders. A defect in the dendritic growth and elaboration of motor neocortical pyramidal neurons in neonates lacking neuregulin-4 (NRG4) has previously been reported. In this study, we investigated if the loss of NRG4 causes further morphological defects that are specific to these neurons. We analysed the soma size of pyramidal neurons of layers 2/3 and 5 of the motor cortex and a subpopulation of multipolar interneurons in this neocortical region in Nrg4+/+ and Nrg4-/- mice. There were significant decreases in pyramidal neuron soma size in Nrg4-/- mice compared with Nrg4+/+ littermates at all stages studied (P10, P30 and P60). The reduction was especially marked at P10 and in layer 5 pyramidal neurons. Soma size was not significantly different for multipolar interneurons at any age. This in vivo phenotype was replicated in pyramidal neurons cultured from Nrg4-/- mice and was rescued by neuregulin-4 treatment. Analysis of a public single-cell RNA sequencing repository revealed discrete Nrg4 and Erbb4 expression in subpopulations of layer 5 pyramidal neurons, suggesting that the observed defects were due in part to loss of autocrine Nrg4/ErbB4 signalling. The pyramidal phenotype in the motor cortex of Nrg4-/- mice was associated with a lack of Rotarod test improvement in P60 mice, suggesting that absence of NRG4 causes alterations in motor performance.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license
Publisher: Society for Neuroscience: eNeuro
ISSN: 2373-2822
Funders: Wellcome Trust
Date of First Compliant Deposit: 24 February 2021
Date of Acceptance: 8 January 2021
Last Modified: 20 May 2021 01:33
URI: http://orca.cardiff.ac.uk/id/eprint/138915

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