Cargando…
Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890462/ https://www.ncbi.nlm.nih.gov/pubmed/31742552 http://dx.doi.org/10.7554/eLife.50617 |
_version_ | 1783475614848647168 |
---|---|
author | Willett, Ryan T Bayin, N Sumru Lee, Andrew S Krishnamurthy, Anjana Wojcinski, Alexandre Lao, Zhimin Stephen, Daniel Rosello-Diez, Alberto Dauber-Decker, Katherine L Orvis, Grant D Wu, Zhuhao Tessier-Lavigne, Marc Joyner, Alexandra L |
author_facet | Willett, Ryan T Bayin, N Sumru Lee, Andrew S Krishnamurthy, Anjana Wojcinski, Alexandre Lao, Zhimin Stephen, Daniel Rosello-Diez, Alberto Dauber-Decker, Katherine L Orvis, Grant D Wu, Zhuhao Tessier-Lavigne, Marc Joyner, Alexandra L |
author_sort | Willett, Ryan T |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6890462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-68904622019-12-06 Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth Willett, Ryan T Bayin, N Sumru Lee, Andrew S Krishnamurthy, Anjana Wojcinski, Alexandre Lao, Zhimin Stephen, Daniel Rosello-Diez, Alberto Dauber-Decker, Katherine L Orvis, Grant D Wu, Zhuhao Tessier-Lavigne, Marc Joyner, Alexandra L eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2019-11-19 /pmc/articles/PMC6890462/ /pubmed/31742552 http://dx.doi.org/10.7554/eLife.50617 Text en © 2019, Willett et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Willett, Ryan T Bayin, N Sumru Lee, Andrew S Krishnamurthy, Anjana Wojcinski, Alexandre Lao, Zhimin Stephen, Daniel Rosello-Diez, Alberto Dauber-Decker, Katherine L Orvis, Grant D Wu, Zhuhao Tessier-Lavigne, Marc Joyner, Alexandra L Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth |
title | Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth |
title_full | Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth |
title_fullStr | Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth |
title_full_unstemmed | Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth |
title_short | Cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic Purkinje cell number and organ growth |
title_sort | cerebellar nuclei excitatory neurons regulate developmental scaling of presynaptic purkinje cell number and organ growth |
topic | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890462/ https://www.ncbi.nlm.nih.gov/pubmed/31742552 http://dx.doi.org/10.7554/eLife.50617 |
work_keys_str_mv | AT willettryant cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT bayinnsumru cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT leeandrews cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT krishnamurthyanjana cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT wojcinskialexandre cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT laozhimin cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT stephendaniel cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT rosellodiezalberto cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT dauberdeckerkatherinel cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT orvisgrantd cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT wuzhuhao cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT tessierlavignemarc cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth AT joyneralexandral cerebellarnucleiexcitatoryneuronsregulatedevelopmentalscalingofpresynapticpurkinjecellnumberandorgangrowth |