Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic purkinje cell number and organ growth

Ryan T. Willett, N. Sumru Bayin, Andrew S. Lee, Anjana Krishnamurthy, Alexandre Wojcinski, Zhimin Lao, Daniel Stephen, Alberto Rosello-Diez, Katherine L. Dauber-Decker, Grant D. Orvis, Zhuhao Wu, Marc Tessier-Lavigne, Alexandra L. Joyner

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

For neural systems to function effectively, the numbers of each cell type must be proportioned properly during development. We found that conditional knockout of the mouse homeobox genes En1 and En2 in the excitatory cerebellar nuclei neurons (eCN) leads to reduced postnatal growth of the cerebellar cortex. A subset of medial and intermediate eCN are lost in the mutants, with an associated cell non-autonomous loss of their presynaptic partner Purkinje cells by birth leading to proportional scaling down of neuron production in the postnatal cerebellar cortex. Genetic killing of embryonic eCN throughout the cerebellum also leads to loss of Purkinje cells and reduced postnatal growth but throughout the cerebellar cortex. Thus, the eCN play a key role in scaling the size of the cerebellum by influencing the survival of their Purkinje cell partners, which in turn regulate production of granule cells and interneurons via the amount of sonic hedgehog secreted.

Original languageEnglish
Article numbere50617
Number of pages27
JournaleLife
Volume8
DOIs
Publication statusPublished - 19 Nov 2019
Externally publishedYes

Cite this