Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth Journal Article
| Authors: | Willett, R. T.; Bayin, N. S.; Lee, A. S.; Krishnamurthy, A.; Wojcinski, A.; Lao, Z.; Stephen, D.; Rosello-Diez, A.; Dauber-Decker, K. L.; Orvis, G. D.; Wu, Z.; Tessier-Lavigne, M.; Joyner, A. L. |
| Article Title: | Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth |
| 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. © 2019, eLife Sciences Publications Ltd. All rights reserved. |
| Keywords: | immunohistochemistry; adult; controlled study; gene sequence; nonhuman; animal cell; mouse; animal tissue; purkinje cell; cell survival; image analysis; sonic hedgehog protein; animal experiment; cohort analysis; genotype; embryo development; cell differentiation; in situ hybridization; granule cell; protein secretion; gene loss; fluorescence microscopy; cell count; motor dysfunction; doxycycline; nervous system development; stereotactic procedure; cerebellum cortex; cell killing; stereology; nervous system; cerebellum nucleus; presynaptic nerve; cerebellum vermis; antigen retrieval; postnatal growth; male; female; article; organ growth; crispr-cas9 system; gene knockout; developmental screening; experimental behavioral test; footprint test; grip strength test |
| Journal Title: | eLife |
| Volume: | 8 |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications Ltd. |
| Date Published: | 2019-11-19 |
| Start Page: | e50617 |
| Language: | English |
| DOI: | 10.7554/eLife.50617 |
| PUBMED: | 31742552 |
| PROVIDER: | scopus |
| PMCID: | PMC6890462 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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