Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability

Jane Quinn, Michael Molinek, Tomasz J. Nowakowski, John O. Mason, David J. Price

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Abstract

Background: Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported; neurons derived from these Pax6-/-ES cells died rapidly after neuronal differentiation in vitro.Results: Here we report the derivation of new lines of Pax6-/-ES cells and the assessment of their ability to survive and differentiate both in vitro and in vivo. Neurons derived from our new Pax6-/-lines were viable and continued to elaborate processes in culture under conditions that resulted in the death of neurons derived from previously reported Pax6-/-ES cell lines. The new lines of Pax6-/-ES cells showed reduced neurogenic potential, mimicking the effects of loss of Pax6 in vivo. We used our new lines to generate Pax6-/-' Pax6+/+chimeras in which the mutant cells survived and displayed the same phenotypes as Pax6-/-cells in Pax6-/-' Pax6+/+chimeras made by embryo aggregation.Conclusions: We suggest that loss of Pax6 from ES cells reduces their neurogenic capacity but does not necessarily result in the death of derived neurons. We offer these new lines as additional tools for those interested in the generation of chimeras and the analysis of in vitro ES cell models of Pax6 function during neuronal differentiation, embryonic and postnatal development.
Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBMC Neuroscience
Volume11
DOIs
Publication statusPublished - 2010

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Embryonic Stem Cells
Neurons
Cell Line
Genes
Embryonic Development
Transcription Factors
Embryonic Structures
Phenotype
Mutation
In Vitro Techniques

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Quinn, Jane ; Molinek, Michael ; Nowakowski, Tomasz J. ; Mason, John O. ; Price, David J. / Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability. In: BMC Neuroscience. 2010 ; Vol. 11. pp. 1-10.
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abstract = "Background: Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported; neurons derived from these Pax6-/-ES cells died rapidly after neuronal differentiation in vitro.Results: Here we report the derivation of new lines of Pax6-/-ES cells and the assessment of their ability to survive and differentiate both in vitro and in vivo. Neurons derived from our new Pax6-/-lines were viable and continued to elaborate processes in culture under conditions that resulted in the death of neurons derived from previously reported Pax6-/-ES cell lines. The new lines of Pax6-/-ES cells showed reduced neurogenic potential, mimicking the effects of loss of Pax6 in vivo. We used our new lines to generate Pax6-/-' Pax6+/+chimeras in which the mutant cells survived and displayed the same phenotypes as Pax6-/-cells in Pax6-/-' Pax6+/+chimeras made by embryo aggregation.Conclusions: We suggest that loss of Pax6 from ES cells reduces their neurogenic capacity but does not necessarily result in the death of derived neurons. We offer these new lines as additional tools for those interested in the generation of chimeras and the analysis of in vitro ES cell models of Pax6 function during neuronal differentiation, embryonic and postnatal development.",
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Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability. / Quinn, Jane; Molinek, Michael; Nowakowski, Tomasz J.; Mason, John O.; Price, David J.

In: BMC Neuroscience, Vol. 11, 2010, p. 1-10.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability

AU - Quinn, Jane

AU - Molinek, Michael

AU - Nowakowski, Tomasz J.

AU - Mason, John O.

AU - Price, David J.

N1 - Imported on 12 Apr 2017 - DigiTool details were: Journal title (773t) = BMC Neuroscience. ISSNs: 1471-2202;

PY - 2010

Y1 - 2010

N2 - Background: Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported; neurons derived from these Pax6-/-ES cells died rapidly after neuronal differentiation in vitro.Results: Here we report the derivation of new lines of Pax6-/-ES cells and the assessment of their ability to survive and differentiate both in vitro and in vivo. Neurons derived from our new Pax6-/-lines were viable and continued to elaborate processes in culture under conditions that resulted in the death of neurons derived from previously reported Pax6-/-ES cell lines. The new lines of Pax6-/-ES cells showed reduced neurogenic potential, mimicking the effects of loss of Pax6 in vivo. We used our new lines to generate Pax6-/-' Pax6+/+chimeras in which the mutant cells survived and displayed the same phenotypes as Pax6-/-cells in Pax6-/-' Pax6+/+chimeras made by embryo aggregation.Conclusions: We suggest that loss of Pax6 from ES cells reduces their neurogenic capacity but does not necessarily result in the death of derived neurons. We offer these new lines as additional tools for those interested in the generation of chimeras and the analysis of in vitro ES cell models of Pax6 function during neuronal differentiation, embryonic and postnatal development.

AB - Background: Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported; neurons derived from these Pax6-/-ES cells died rapidly after neuronal differentiation in vitro.Results: Here we report the derivation of new lines of Pax6-/-ES cells and the assessment of their ability to survive and differentiate both in vitro and in vivo. Neurons derived from our new Pax6-/-lines were viable and continued to elaborate processes in culture under conditions that resulted in the death of neurons derived from previously reported Pax6-/-ES cell lines. The new lines of Pax6-/-ES cells showed reduced neurogenic potential, mimicking the effects of loss of Pax6 in vivo. We used our new lines to generate Pax6-/-' Pax6+/+chimeras in which the mutant cells survived and displayed the same phenotypes as Pax6-/-cells in Pax6-/-' Pax6+/+chimeras made by embryo aggregation.Conclusions: We suggest that loss of Pax6 from ES cells reduces their neurogenic capacity but does not necessarily result in the death of derived neurons. We offer these new lines as additional tools for those interested in the generation of chimeras and the analysis of in vitro ES cell models of Pax6 function during neuronal differentiation, embryonic and postnatal development.

KW - Open access version available

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SP - 1

EP - 10

JO - BMC Neuroscience

JF - BMC Neuroscience

SN - 1471-2202

ER -