A directional 3D neurite outgrowth model for studying motor axon biology and disease

Abstract We report a method to generate a 3D motor neuron model with segregated and directed axonal outgrowth. iPSC-derived motor neurons are cultured in extracellular matrix gel in a microfluidic platform. Neurons extend their axons into an adjacent layer of gel, whereas dendrites and soma remain p...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Xandor M. Spijkers, Svetlana Pasteuning-Vuhman, Jennifa C. Dorleijn, Paul Vulto, Nienke R. Wevers, R. Jeroen Pasterkamp
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d11774b7f2654065b86858fe12f68e23
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d11774b7f2654065b86858fe12f68e23
record_format	dspace
spelling	oai:doaj.org-article:d11774b7f2654065b86858fe12f68e232021-12-02T11:50:30ZA directional 3D neurite outgrowth model for studying motor axon biology and disease10.1038/s41598-021-81335-z2045-2322https://doaj.org/article/d11774b7f2654065b86858fe12f68e232021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81335-zhttps://doaj.org/toc/2045-2322Abstract We report a method to generate a 3D motor neuron model with segregated and directed axonal outgrowth. iPSC-derived motor neurons are cultured in extracellular matrix gel in a microfluidic platform. Neurons extend their axons into an adjacent layer of gel, whereas dendrites and soma remain predominantly in the somal compartment, as verified by immunofluorescent staining. Axonal outgrowth could be precisely quantified and was shown to respond to the chemotherapeutic drug vincristine in a highly reproducible dose-dependent manner. The model was shown susceptible to excitotoxicity upon exposure with excess glutamate and showed formation of stress granules upon excess glutamate or sodium arsenite exposure, mimicking processes common in motor neuron diseases. Importantly, outgrowing axons could be attracted and repelled through a gradient of axonal guidance cues, such as semaphorins. The platform comprises 40 chips arranged underneath a microtiter plate providing both throughput and compatibility to standard laboratory equipment. The model will thus prove ideal for studying axonal biology and disease, drug discovery and regenerative medicine.Xandor M. SpijkersSvetlana Pasteuning-VuhmanJennifa C. DorleijnPaul VultoNienke R. WeversR. Jeroen PasterkampNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xandor M. Spijkers Svetlana Pasteuning-Vuhman Jennifa C. Dorleijn Paul Vulto Nienke R. Wevers R. Jeroen Pasterkamp A directional 3D neurite outgrowth model for studying motor axon biology and disease
description	Abstract We report a method to generate a 3D motor neuron model with segregated and directed axonal outgrowth. iPSC-derived motor neurons are cultured in extracellular matrix gel in a microfluidic platform. Neurons extend their axons into an adjacent layer of gel, whereas dendrites and soma remain predominantly in the somal compartment, as verified by immunofluorescent staining. Axonal outgrowth could be precisely quantified and was shown to respond to the chemotherapeutic drug vincristine in a highly reproducible dose-dependent manner. The model was shown susceptible to excitotoxicity upon exposure with excess glutamate and showed formation of stress granules upon excess glutamate or sodium arsenite exposure, mimicking processes common in motor neuron diseases. Importantly, outgrowing axons could be attracted and repelled through a gradient of axonal guidance cues, such as semaphorins. The platform comprises 40 chips arranged underneath a microtiter plate providing both throughput and compatibility to standard laboratory equipment. The model will thus prove ideal for studying axonal biology and disease, drug discovery and regenerative medicine.
format	article
author	Xandor M. Spijkers Svetlana Pasteuning-Vuhman Jennifa C. Dorleijn Paul Vulto Nienke R. Wevers R. Jeroen Pasterkamp
author_facet	Xandor M. Spijkers Svetlana Pasteuning-Vuhman Jennifa C. Dorleijn Paul Vulto Nienke R. Wevers R. Jeroen Pasterkamp
author_sort	Xandor M. Spijkers
title	A directional 3D neurite outgrowth model for studying motor axon biology and disease
title_short	A directional 3D neurite outgrowth model for studying motor axon biology and disease
title_full	A directional 3D neurite outgrowth model for studying motor axon biology and disease
title_fullStr	A directional 3D neurite outgrowth model for studying motor axon biology and disease
title_full_unstemmed	A directional 3D neurite outgrowth model for studying motor axon biology and disease
title_sort	directional 3d neurite outgrowth model for studying motor axon biology and disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d11774b7f2654065b86858fe12f68e23
work_keys_str_mv	AT xandormspijkers adirectional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT svetlanapasteuningvuhman adirectional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT jennifacdorleijn adirectional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT paulvulto adirectional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT nienkerwevers adirectional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT rjeroenpasterkamp adirectional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT xandormspijkers directional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT svetlanapasteuningvuhman directional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT jennifacdorleijn directional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT paulvulto directional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT nienkerwevers directional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease AT rjeroenpasterkamp directional3dneuriteoutgrowthmodelforstudyingmotoraxonbiologyanddisease
_version_	1718395192237621248

A directional 3D neurite outgrowth model for studying motor axon biology and disease

Ejemplares similares