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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
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