CD40 is a major regulator of dendrite growth from developing excitatory and inhibitory neurons

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Abstract

Dendrite size and morphology are key determinants of the functional properties of neurons and neural circuits. Here we show that CD40, a member of the TNF receptor superfamily, is a major regulator of dendrite growth and elaboration in the developing brain. The dendrites of hippocampal excitatory neurons were markedly stunted in Cd40^-/- mice, whereas those of striatal inhibitory neurons were much more exuberant. These striking and opposite phenotypic changes were also observed in excitatory and inhibitory neurons cultured from Cd40^-/- mice and were rescued by soluble CD40. The changes in excitatory and inhibitory neurons cultured from Cd40^-/- mice were mimicked in neurons of Cd40^+/+ mice by treatment with soluble CD40L and were dependent on PKC-b and PKC-g, respectively. These results suggest that CD40-activated CD40L reverse signalling has striking and opposite effects on the growth and elaboration of dendrites among major classes of brain neurons by PKC-dependent mechanisms.

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Paulina Carriba

School of Biosciences, Cardiff University, Cardiff, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Alun M Davies

School of Biosciences, Cardiff University, Cardiff, United Kingdom

For correspondence
DaviesAlun@cardiff.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5841-8176

Funding

Wellcome Trust (103852)

Alun M Davies

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Mouse breeding and housing was approved by the Cardiff University Ethical Review Board and was performed within the remit of Home Office Licence PPL303081.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.