Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar Cortex

Purkinje cells (PCs) are large GABAergic projection neurons of the cerebellar cortex, endowed with elaborate dendrites that receive a multitude of excitatory inputs. Being the only efferent neuron of the cerebellar cortex, PCs project to cerebellar nuclei and control behaviors ranging from movement...

Full description

Bibliographic Details
Main Authors: Shahin Shabanipour, Xiaodan Jiao, Maryam Rahimi-Balaei, Mohamad Reza Aghanoori, Seung H. Chung, Saeid Ghavami, G. Giacomo Consalez, Hassan Marzban
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-01-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2021.804402/full
_version_ 1798016130779971584
author Shahin Shabanipour
Xiaodan Jiao
Maryam Rahimi-Balaei
Mohamad Reza Aghanoori
Seung H. Chung
Saeid Ghavami
G. Giacomo Consalez
Hassan Marzban
Hassan Marzban
author_facet Shahin Shabanipour
Xiaodan Jiao
Maryam Rahimi-Balaei
Mohamad Reza Aghanoori
Seung H. Chung
Saeid Ghavami
G. Giacomo Consalez
Hassan Marzban
Hassan Marzban
author_sort Shahin Shabanipour
collection DOAJ
description Purkinje cells (PCs) are large GABAergic projection neurons of the cerebellar cortex, endowed with elaborate dendrites that receive a multitude of excitatory inputs. Being the only efferent neuron of the cerebellar cortex, PCs project to cerebellar nuclei and control behaviors ranging from movement to cognition and social interaction. Neural cell adhesion molecule 1 (NCAM1) is widely expressed in the embryonic and postnatal development of the brain and plays essential roles in neuronal migration, axon pathfinding and synapse assembly. However, despite its high expression levels in cerebellum, little is known to date regarding the role(s) of NCAM1 in PCs development. Among other aspects, elucidating how the expression of NCAM1 in PCs could impact their postnatal migration would be a significant achievement. We analyzed the Acp2 mutant mouse (nax: naked and ataxia), which displays excessive PC migration into the molecular layer, and investigated how the excessive migration of PCs along Bergmann glia could correlate to NCAM1 expression pattern in early postnatal days. Our Western blot and RT-qPCR analysis of the whole cerebellum show that the protein and mRNA of NCAM1 in wild type are not different during PC dispersal from the cluster stage to monolayer formation. However, RT-qPCR analysis from FACS-based isolated PCs shows that Ncam1 is significantly upregulated when PCs fail to align and instead overmigrate into the molecular layer. Our results suggest two alternative interpretations: (1) NCAM1 promotes excessive PC migration along Bergmann glia, or (2) NCAM1 upregulation is an attempt to prevent PCs from invading the molecular layer. If the latter scenario proves true, NCAM1 may play a key role in PC monolayer formation.
first_indexed 2024-04-11T15:44:59Z
format Article
id doaj.art-a5a4e4a2c27d4eeca4bc4d1e6bf6ba85
institution Directory Open Access Journal
issn 1662-453X
language English
last_indexed 2024-04-11T15:44:59Z
publishDate 2022-01-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Neuroscience
spelling doaj.art-a5a4e4a2c27d4eeca4bc4d1e6bf6ba852022-12-22T04:15:36ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-01-011510.3389/fnins.2021.804402804402Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar CortexShahin Shabanipour0Xiaodan Jiao1Maryam Rahimi-Balaei2Mohamad Reza Aghanoori3Seung H. Chung4Saeid Ghavami5G. Giacomo Consalez6Hassan Marzban7Hassan Marzban8Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Oral Biology, University of Illinois Chicago, Chicago, IL, United StatesDepartment of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaDivision of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, ItalyDepartment of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaThe Children’s Hospital Research Institute of Manitoba (CHRIM), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaPurkinje cells (PCs) are large GABAergic projection neurons of the cerebellar cortex, endowed with elaborate dendrites that receive a multitude of excitatory inputs. Being the only efferent neuron of the cerebellar cortex, PCs project to cerebellar nuclei and control behaviors ranging from movement to cognition and social interaction. Neural cell adhesion molecule 1 (NCAM1) is widely expressed in the embryonic and postnatal development of the brain and plays essential roles in neuronal migration, axon pathfinding and synapse assembly. However, despite its high expression levels in cerebellum, little is known to date regarding the role(s) of NCAM1 in PCs development. Among other aspects, elucidating how the expression of NCAM1 in PCs could impact their postnatal migration would be a significant achievement. We analyzed the Acp2 mutant mouse (nax: naked and ataxia), which displays excessive PC migration into the molecular layer, and investigated how the excessive migration of PCs along Bergmann glia could correlate to NCAM1 expression pattern in early postnatal days. Our Western blot and RT-qPCR analysis of the whole cerebellum show that the protein and mRNA of NCAM1 in wild type are not different during PC dispersal from the cluster stage to monolayer formation. However, RT-qPCR analysis from FACS-based isolated PCs shows that Ncam1 is significantly upregulated when PCs fail to align and instead overmigrate into the molecular layer. Our results suggest two alternative interpretations: (1) NCAM1 promotes excessive PC migration along Bergmann glia, or (2) NCAM1 upregulation is an attempt to prevent PCs from invading the molecular layer. If the latter scenario proves true, NCAM1 may play a key role in PC monolayer formation.https://www.frontiersin.org/articles/10.3389/fnins.2021.804402/fullBergmann glianaxneuronal migrationPurkinje cell clustermice
spellingShingle Shahin Shabanipour
Xiaodan Jiao
Maryam Rahimi-Balaei
Mohamad Reza Aghanoori
Seung H. Chung
Saeid Ghavami
G. Giacomo Consalez
Hassan Marzban
Hassan Marzban
Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar Cortex
Frontiers in Neuroscience
Bergmann glia
nax
neuronal migration
Purkinje cell cluster
mice
title Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar Cortex
title_full Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar Cortex
title_fullStr Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar Cortex
title_full_unstemmed Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar Cortex
title_short Upregulation of Neural Cell Adhesion Molecule 1 and Excessive Migration of Purkinje Cells in Cerebellar Cortex
title_sort upregulation of neural cell adhesion molecule 1 and excessive migration of purkinje cells in cerebellar cortex
topic Bergmann glia
nax
neuronal migration
Purkinje cell cluster
mice
url https://www.frontiersin.org/articles/10.3389/fnins.2021.804402/full
work_keys_str_mv AT shahinshabanipour upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex
AT xiaodanjiao upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex
AT maryamrahimibalaei upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex
AT mohamadrezaaghanoori upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex
AT seunghchung upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex
AT saeidghavami upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex
AT ggiacomoconsalez upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex
AT hassanmarzban upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex
AT hassanmarzban upregulationofneuralcelladhesionmolecule1andexcessivemigrationofpurkinjecellsincerebellarcortex