Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth
- Memorial Sloan Kettering Cancer Center, United States
- The Rockefeller University, United States
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.
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No datasets were generated.
Article and author information
Author details
Alexandra L Joyner
Funding
National Institute of Mental Health (R37MH085726)
- Alexandra L Joyner
National Institute of Neurological Disorders and Stroke (R01NS092096)
- Alexandra L Joyner
National Cancer Institute (P30CA008748-48)
- Alexandra L Joyner
National Institute of Neurological Disorders and Stroke (F32NS080422)
- Ryan T Willett
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) under an approved protocol from MSKCC (Protocol no: 07-01-001).
Copyright
© 2019, Willett et al.
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.
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Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth
eLife 8:e50617.
https://doi.org/10.7554/eLife.50617
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