---
_id: '7814'
abstract:
- lang: eng
text: 'Scientific research is to date largely restricted to wealthy laboratories
in developed nations due to the necessity of complex and expensive equipment.
This inequality limits the capacity of science to be used as a diplomatic channel.
Maker movements use open-source technologies including additive manufacturing
(3D printing) and laser cutting, together with low-cost computers for developing
novel products. This movement is setting the groundwork for a revolution, allowing
scientific equipment to be sourced at a fraction of the cost and has the potential
to increase the availability of equipment for scientists around the world. Science
education is increasingly recognized as another channel for science diplomacy.
In this perspective, we introduce the idea that the Maker movement and open-source
technologies have the potential to revolutionize science, technology, engineering
and mathematics (STEM) education worldwide. We present an open-source STEM didactic
tool called SCOPES (Sparking Curiosity through Open-source Platforms in Education
and Science). SCOPES is self-contained, independent of local resources, and cost-effective.
SCOPES can be adapted to communicate complex subjects from genetics to neurobiology,
perform real-world biological experiments and explore digitized scientific samples.
We envision such platforms will enhance science diplomacy by providing a means
for scientists to share their findings with classrooms and for educators to incorporate
didactic concepts into STEM lessons. By providing students the opportunity to
design, perform, and share scientific experiments, students also experience firsthand
the benefits of a multinational scientific community. We provide instructions
on how to build and use SCOPES on our webpage: http://scopeseducation.org.'
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
- _id: EM-Fac
article_number: '48'
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
citation:
ama: 'Beattie RJ, Hippenmeyer S, Pauler F. SCOPES: Sparking curiosity through Open-Source
platforms in education and science. Frontiers in Education. 2020;5. doi:10.3389/feduc.2020.00048'
apa: 'Beattie, R. J., Hippenmeyer, S., & Pauler, F. (2020). SCOPES: Sparking
curiosity through Open-Source platforms in education and science. Frontiers
in Education. Frontiers Media. https://doi.org/10.3389/feduc.2020.00048'
chicago: 'Beattie, Robert J, Simon Hippenmeyer, and Florian Pauler. “SCOPES: Sparking
Curiosity through Open-Source Platforms in Education and Science.” Frontiers
in Education. Frontiers Media, 2020. https://doi.org/10.3389/feduc.2020.00048.'
ieee: 'R. J. Beattie, S. Hippenmeyer, and F. Pauler, “SCOPES: Sparking curiosity
through Open-Source platforms in education and science,” Frontiers in Education,
vol. 5. Frontiers Media, 2020.'
ista: 'Beattie RJ, Hippenmeyer S, Pauler F. 2020. SCOPES: Sparking curiosity through
Open-Source platforms in education and science. Frontiers in Education. 5, 48.'
mla: 'Beattie, Robert J., et al. “SCOPES: Sparking Curiosity through Open-Source
Platforms in Education and Science.” Frontiers in Education, vol. 5, 48,
Frontiers Media, 2020, doi:10.3389/feduc.2020.00048.'
short: R.J. Beattie, S. Hippenmeyer, F. Pauler, Frontiers in Education 5 (2020).
corr_author: '1'
date_created: 2020-05-11T08:18:48Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2024-10-22T10:46:38Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3389/feduc.2020.00048
ec_funded: 1
file:
- access_level: open_access
checksum: a24ec24e38d843341ae620ec76c53688
content_type: application/pdf
creator: dernst
date_created: 2020-05-11T11:34:08Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7818'
file_name: 2020_FrontiersEduc_Beattie.pdf
file_size: 1402146
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
intvolume: ' 5'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Frontiers in Education
publication_identifier:
issn:
- 2504-284X
publication_status: published
publisher: Frontiers Media
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'SCOPES: Sparking curiosity through Open-Source platforms in education and
science'
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2020'
...
---
_id: '8162'
abstract:
- lang: eng
text: In mammalian genomes, a subset of genes is regulated by genomic imprinting,
resulting in silencing of one parental allele. Imprinting is essential for cerebral
cortex development, but prevalence and functional impact in individual cells is
unclear. Here, we determined allelic expression in cortical cell types and established
a quantitative platform to interrogate imprinting in single cells. We created
cells with uniparental chromosome disomy (UPD) containing two copies of either
the maternal or the paternal chromosome; hence, imprinted genes will be 2-fold
overexpressed or not expressed. By genetic labeling of UPD, we determined cellular
phenotypes and transcriptional responses to deregulated imprinted gene expression
at unprecedented single-cell resolution. We discovered an unexpected degree of
cell-type specificity and a novel function of imprinting in the regulation of
cortical astrocyte survival. More generally, our results suggest functional relevance
of imprinted gene expression in glial astrocyte lineage and thus for generating
cortical cell-type diversity.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), and A. Seitz and P. Moll (Lexogen GmbH) for technical
support; G. Arque, S. Resch, C. Igler, C. Dotter, C. Yahya, Q. Hudson, and D. Andergassen
for initial experiments and/or assistance; D. Barlow, O. Bell, and all members of
the Hippenmeyer lab for discussion; and N. Barton, B. Vicoso, M. Sixt, and L. Luo
for comments on earlier versions of the manuscript. This research was supported
by the Scientific Service Units (SSU) of IST Austria through resources provided
by the Bioimaging Facilities (BIF), Life Science Facilities (LSF), and Preclinical
Facilities (PCF). A.H.H. is a recipient of a DOC fellowship (24812) of the Austrian
Academy of Sciences. N.A. received support from the FWF Firnberg-Programm (T 1031).
R.B. received support from the FWF Meitner-Programm (M 2416). This work was also
supported by IST Austria institutional funds; a NÖ Forschung und Bildung n[f+b]
life science call grant (C13-002) to S.H.; a program grant from the Human Frontiers
Science Program (RGP0053/2014) to S.H.; the People Programme (Marie Curie Actions)
of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant
agreement 618444 to S.H.; and the European Research Council (ERC) under the European
Union’s Horizon 2020 research and innovation program (grant agreement 725780 LinPro)
to S.H.
article_processing_charge: No
article_type: original
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Thomas
full_name: Penz, Thomas
last_name: Penz
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
orcid: 0000-0001-6091-3088
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Laukoter S, Pauler F, Beattie RJ, et al. Cell-type specificity of genomic imprinting
in cerebral cortex. Neuron. 2020;107(6):1160-1179.e9. doi:10.1016/j.neuron.2020.06.031
apa: Laukoter, S., Pauler, F., Beattie, R. J., Amberg, N., Hansen, A. H., Streicher,
C., … Hippenmeyer, S. (2020). Cell-type specificity of genomic imprinting in cerebral
cortex. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.06.031
chicago: Laukoter, Susanne, Florian Pauler, Robert J Beattie, Nicole Amberg, Andi
H Hansen, Carmen Streicher, Thomas Penz, Christoph Bock, and Simon Hippenmeyer.
“Cell-Type Specificity of Genomic Imprinting in Cerebral Cortex.” Neuron.
Elsevier, 2020. https://doi.org/10.1016/j.neuron.2020.06.031.
ieee: S. Laukoter et al., “Cell-type specificity of genomic imprinting in
cerebral cortex,” Neuron, vol. 107, no. 6. Elsevier, p. 1160–1179.e9, 2020.
ista: Laukoter S, Pauler F, Beattie RJ, Amberg N, Hansen AH, Streicher C, Penz T,
Bock C, Hippenmeyer S. 2020. Cell-type specificity of genomic imprinting in cerebral
cortex. Neuron. 107(6), 1160–1179.e9.
mla: Laukoter, Susanne, et al. “Cell-Type Specificity of Genomic Imprinting in Cerebral
Cortex.” Neuron, vol. 107, no. 6, Elsevier, 2020, p. 1160–1179.e9, doi:10.1016/j.neuron.2020.06.031.
short: S. Laukoter, F. Pauler, R.J. Beattie, N. Amberg, A.H. Hansen, C. Streicher,
T. Penz, C. Bock, S. Hippenmeyer, Neuron 107 (2020) 1160–1179.e9.
corr_author: '1'
date_created: 2020-07-23T16:03:12Z
date_published: 2020-09-23T00:00:00Z
date_updated: 2025-06-12T07:19:46Z
day: '23'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2020.06.031
ec_funded: 1
external_id:
isi:
- '000579698700006'
pmid:
- '32707083'
file:
- access_level: open_access
checksum: 7becdc16a6317304304631087ae7dd7f
content_type: application/pdf
creator: dernst
date_created: 2020-12-02T09:26:46Z
date_updated: 2020-12-02T09:26:46Z
file_id: '8828'
file_name: 2020_Neuron_Laukoter.pdf
file_size: 8911830
relation: main_file
success: 1
file_date_updated: 2020-12-02T09:26:46Z
has_accepted_license: '1'
intvolume: ' 107'
isi: 1
issue: '6'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 1160-1179.e9
pmid: 1
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular mechanisms of radial neuronal migration
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T01031
name: Role of Eed in neural stem cell lineage progression
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
- _id: 25D7962E-B435-11E9-9278-68D0E5697425
grant_number: RGP0053/2014
name: Quantitative Structure-Function Analysis of Cerebral Cortex Assembly at Clonal
Level
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Website
relation: press_release
url: https://ist.ac.at/en/news/cells-react-differently-to-genomic-imprinting/
scopus_import: '1'
status: public
title: Cell-type specificity of genomic imprinting in cerebral cortex
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 107
year: '2020'
...
---
_id: '8949'
abstract:
- lang: eng
text: Development of the nervous system undergoes important transitions,
including one from neurogenesis to gliogenesis which occurs late during embryonic
gestation. Here we report on clonal analysis of gliogenesis in mice using Mosaic
Analysis with Double Markers (MADM) with quantitative and computational methods.
Results reveal that developmental gliogenesis in the cerebral cortex occurs in
a fraction of earlier neurogenic clones, accelerating around E16.5, and giving
rise to both astrocytes and oligodendrocytes. Moreover, MADM-based genetic deletion
of the epidermal growth factor receptor (Egfr) in gliogenic clones revealed that
Egfr is cell autonomously required for gliogenesis in the mouse dorsolateral cortices.
A broad range in the proliferation capacity, symmetry of clones, and competitive
advantage of MADM cells was evident in clones that contained one cellular lineage
with double dosage of Egfr relative to their environment, while their sibling
Egfr-null cells failed to generate glia. Remarkably, the total numbers of glia
in MADM clones balance out regardless of significant alterations in clonal symmetries.
The variability in glial clones shows stochastic patterns that we define mathematically,
which are different from the deterministic patterns in neuronal clones. This study
sets a foundation for studying the biological significance of stochastic and deterministic
clonal principles underlying tissue development, and identifying mechanisms that
differentiate between neurogenesis and gliogenesis.
acknowledgement: This research was funded by grants from the National Institutes of
Health to H.T.G. (R01NS098370 and R01NS089795). C.V.M. was supported by a National
Science Foundation Graduate Research Fellowship (DGE-1746939). R.B. was supported
by the FWF Lise-Meitner program (M 2416), and S.H. was supported by the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
programme (grant agreement No 725780 LinPro).The authors thank members of the Ghashghaei
lab for discussions, technical support, and help with preparation of the manuscript.
article_number: '2662'
article_processing_charge: No
article_type: original
author:
- first_name: Xuying
full_name: Zhang, Xuying
last_name: Zhang
- first_name: Christine V.
full_name: Mennicke, Christine V.
last_name: Mennicke
- first_name: Guanxi
full_name: Xiao, Guanxi
last_name: Xiao
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Mansoor
full_name: Haider, Mansoor
last_name: Haider
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: H. Troy
full_name: Ghashghaei, H. Troy
last_name: Ghashghaei
citation:
ama: Zhang X, Mennicke CV, Xiao G, et al. Clonal analysis of gliogenesis in the
cerebral cortex reveals stochastic expansion of glia and cell autonomous responses
to Egfr dosage. Cells. 2020;9(12). doi:10.3390/cells9122662
apa: Zhang, X., Mennicke, C. V., Xiao, G., Beattie, R. J., Haider, M., Hippenmeyer,
S., & Ghashghaei, H. T. (2020). Clonal analysis of gliogenesis in the cerebral
cortex reveals stochastic expansion of glia and cell autonomous responses to Egfr
dosage. Cells. MDPI. https://doi.org/10.3390/cells9122662
chicago: Zhang, Xuying, Christine V. Mennicke, Guanxi Xiao, Robert J Beattie, Mansoor
Haider, Simon Hippenmeyer, and H. Troy Ghashghaei. “Clonal Analysis of Gliogenesis
in the Cerebral Cortex Reveals Stochastic Expansion of Glia and Cell Autonomous
Responses to Egfr Dosage.” Cells. MDPI, 2020. https://doi.org/10.3390/cells9122662.
ieee: X. Zhang et al., “Clonal analysis of gliogenesis in the cerebral cortex
reveals stochastic expansion of glia and cell autonomous responses to Egfr dosage,”
Cells, vol. 9, no. 12. MDPI, 2020.
ista: Zhang X, Mennicke CV, Xiao G, Beattie RJ, Haider M, Hippenmeyer S, Ghashghaei
HT. 2020. Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic
expansion of glia and cell autonomous responses to Egfr dosage. Cells. 9(12),
2662.
mla: Zhang, Xuying, et al. “Clonal Analysis of Gliogenesis in the Cerebral Cortex
Reveals Stochastic Expansion of Glia and Cell Autonomous Responses to Egfr Dosage.”
Cells, vol. 9, no. 12, 2662, MDPI, 2020, doi:10.3390/cells9122662.
short: X. Zhang, C.V. Mennicke, G. Xiao, R.J. Beattie, M. Haider, S. Hippenmeyer,
H.T. Ghashghaei, Cells 9 (2020).
date_created: 2020-12-14T08:04:03Z
date_published: 2020-12-11T00:00:00Z
date_updated: 2025-06-12T07:02:43Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3390/cells9122662
ec_funded: 1
external_id:
isi:
- '000601787300001'
pmid:
- '33322301'
file:
- access_level: open_access
checksum: 5095cbdc728c9a510c5761cf60a8861c
content_type: application/pdf
creator: dernst
date_created: 2020-12-14T08:09:43Z
date_updated: 2020-12-14T08:09:43Z
file_id: '8950'
file_name: 2020_Cells_Zhang.pdf
file_size: 3504525
relation: main_file
success: 1
file_date_updated: 2020-12-14T08:09:43Z
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cells
publication_identifier:
issn:
- 2073-4409
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: Clonal analysis of gliogenesis in the cerebral cortex reveals stochastic expansion
of glia and cell autonomous responses to Egfr dosage
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9
year: '2020'
...
---
_id: '7253'
abstract:
- lang: eng
text: The cyclin-dependent kinase inhibitor p57KIP2 is encoded by the imprinted
Cdkn1c locus, exhibits maternal expression, and is essential for cerebral cortex
development. How Cdkn1c regulates corticogenesis is however not clear. To this
end we employ Mosaic Analysis with Double Markers (MADM) technology to genetically
dissect Cdkn1c gene function in corticogenesis at single cell resolution. We find
that the previously described growth-inhibitory Cdkn1c function is a non-cell-autonomous
one, acting on the whole organism. In contrast we reveal a growth-promoting cell-autonomous
Cdkn1c function which at the mechanistic level mediates radial glial progenitor
cell and nascent projection neuron survival. Strikingly, the growth-promoting
function of Cdkn1c is highly dosage sensitive but not subject to genomic imprinting.
Collectively, our results suggest that the Cdkn1c locus regulates cortical development
through distinct cell-autonomous and non-cell-autonomous mechanisms. More generally,
our study highlights the importance to probe the relative contributions of cell
intrinsic gene function and tissue-wide mechanisms to the overall phenotype.
acknowledged_ssus:
- _id: PreCl
article_number: '195'
article_processing_charge: No
article_type: original
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Keiichi I.
full_name: Nakayama, Keiichi I.
last_name: Nakayama
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. Imprinted
Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral cortex
development. Nature Communications. 2020;11. doi:10.1038/s41467-019-14077-2
apa: Laukoter, S., Beattie, R. J., Pauler, F., Amberg, N., Nakayama, K. I., &
Hippenmeyer, S. (2020). Imprinted Cdkn1c genomic locus cell-autonomously promotes
cell survival in cerebral cortex development. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-019-14077-2
chicago: Laukoter, Susanne, Robert J Beattie, Florian Pauler, Nicole Amberg, Keiichi
I. Nakayama, and Simon Hippenmeyer. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously
Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-019-14077-2.
ieee: S. Laukoter, R. J. Beattie, F. Pauler, N. Amberg, K. I. Nakayama, and S. Hippenmeyer,
“Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral
cortex development,” Nature Communications, vol. 11. Springer Nature, 2020.
ista: Laukoter S, Beattie RJ, Pauler F, Amberg N, Nakayama KI, Hippenmeyer S. 2020.
Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in cerebral
cortex development. Nature Communications. 11, 195.
mla: Laukoter, Susanne, et al. “Imprinted Cdkn1c Genomic Locus Cell-Autonomously
Promotes Cell Survival in Cerebral Cortex Development.” Nature Communications,
vol. 11, 195, Springer Nature, 2020, doi:10.1038/s41467-019-14077-2.
short: S. Laukoter, R.J. Beattie, F. Pauler, N. Amberg, K.I. Nakayama, S. Hippenmeyer,
Nature Communications 11 (2020).
corr_author: '1'
date_created: 2020-01-11T10:42:48Z
date_published: 2020-01-10T00:00:00Z
date_updated: 2025-06-12T07:30:49Z
day: '10'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41467-019-14077-2
ec_funded: 1
external_id:
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pmid:
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language:
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month: '01'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T01031
name: Role of Eed in neural stem cell lineage progression
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/new-function-for-potential-tumour-suppressor-in-brain-development/
scopus_import: '1'
status: public
title: Imprinted Cdkn1c genomic locus cell-autonomously promotes cell survival in
cerebral cortex development
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2020'
...
---
_id: '7815'
abstract:
- lang: eng
text: Beginning from a limited pool of progenitors, the mammalian cerebral cortex
forms highly organized functional neural circuits. However, the underlying cellular
and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs)
and eventual production of neurons and glia in the developing neuroepithelium
remains unclear. Methods to trace NSC division patterns and map the lineage of
clonally related cells have advanced dramatically. However, many contemporary
lineage tracing techniques suffer from the lack of cellular resolution of progeny
cell fate, which is essential for deciphering progenitor cell division patterns.
Presented is a protocol using mosaic analysis with double markers (MADM) to perform
in vivo clonal analysis. MADM concomitantly manipulates individual progenitor
cells and visualizes precise division patterns and lineage progression at unprecedented
single cell resolution. MADM-based interchromosomal recombination events during
the G2-X phase of mitosis, together with temporally inducible CreERT2, provide
exact information on the birth dates of clones and their division patterns. Thus,
MADM lineage tracing provides unprecedented qualitative and quantitative optical
readouts of the proliferation mode of stem cell progenitors at the single cell
level. MADM also allows for examination of the mechanisms and functional requirements
of candidate genes in NSC lineage progression. This method is unique in that comparative
analysis of control and mutant subclones can be performed in the same tissue environment
in vivo. Here, the protocol is described in detail, and experimental paradigms
to employ MADM for clonal analysis and lineage tracing in the developing cerebral
cortex are demonstrated. Importantly, this protocol can be adapted to perform
MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver
is present.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
article_number: e61147
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis
in developing cerebral cortex using mosaic analysis with double markers (MADM).
Journal of Visual Experiments. 2020;(159). doi:10.3791/61147
apa: Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen,
A. H., & Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM). Journal of
Visual Experiments. MyJove Corporation. https://doi.org/10.3791/61147
chicago: Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena
Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis
in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).”
Journal of Visual Experiments. MyJove Corporation, 2020. https://doi.org/10.3791/61147.
ieee: R. J. Beattie et al., “Lineage tracing and clonal analysis in developing
cerebral cortex using mosaic analysis with double markers (MADM),” Journal
of Visual Experiments, no. 159. MyJove Corporation, 2020.
ista: Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer
S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using
mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159),
e61147.
mla: Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing
Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” Journal
of Visual Experiments, no. 159, e61147, MyJove Corporation, 2020, doi:10.3791/61147.
short: R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen,
S. Hippenmeyer, Journal of Visual Experiments (2020).
corr_author: '1'
date_created: 2020-05-11T08:31:20Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2026-04-27T22:30:56Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3791/61147
ec_funded: 1
external_id:
isi:
- '000546406600043'
pmid:
- '32449730'
file:
- access_level: open_access
checksum: 3154ea7f90b9fb45e084cd1c2770597d
content_type: application/pdf
creator: rbeattie
date_created: 2020-05-11T08:28:38Z
date_updated: 2020-07-14T12:48:03Z
file_id: '7816'
file_name: jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf
file_size: 1352186
relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
isi: 1
issue: '159'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T01031
name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular mechanisms of radial neuronal migration
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Journal of Visual Experiments
publication_identifier:
issn:
- 1940-087X
publication_status: published
publisher: MyJove Corporation
quality_controlled: '1'
related_material:
record:
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relation: part_of_dissertation
status: public
scopus_import: '1'
status: public
title: Lineage tracing and clonal analysis in developing cerebral cortex using mosaic
analysis with double markers (MADM)
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7202'
abstract:
- lang: eng
text: The cerebral cortex contains multiple areas with distinctive cytoarchitectonical
patterns, but the cellular mechanisms underlying the emergence of this diversity
remain unclear. Here, we have investigated the neuronal output of individual progenitor
cells in the developing mouse neocortex using a combination of methods that together
circumvent the biases and limitations of individual approaches. Our experimental
results indicate that progenitor cells generate pyramidal cell lineages with a
wide range of sizes and laminar configurations. Mathematical modelling indicates
that these outcomes are compatible with a stochastic model of cortical neurogenesis
in which progenitor cells undergo a series of probabilistic decisions that lead
to the specification of very heterogeneous progenies. Our findings support a mechanism
for cortical neurogenesis whose flexibility would make it capable to generate
the diverse cytoarchitectures that characterize distinct neocortical areas.
article_number: e51381
article_processing_charge: No
article_type: original
author:
- first_name: Alfredo
full_name: Llorca, Alfredo
last_name: Llorca
- first_name: Gabriele
full_name: Ciceri, Gabriele
last_name: Ciceri
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Fong Kuan
full_name: Wong, Fong Kuan
last_name: Wong
- first_name: Giovanni
full_name: Diana, Giovanni
last_name: Diana
- first_name: Eleni
full_name: Serafeimidou-Pouliou, Eleni
last_name: Serafeimidou-Pouliou
- first_name: Marian
full_name: Fernández-Otero, Marian
last_name: Fernández-Otero
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Sebastian J.
full_name: Arnold, Sebastian J.
last_name: Arnold
- first_name: Martin
full_name: Meyer, Martin
last_name: Meyer
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Miguel
full_name: Maravall, Miguel
last_name: Maravall
- first_name: Oscar
full_name: Marín, Oscar
last_name: Marín
citation:
ama: Llorca A, Ciceri G, Beattie RJ, et al. A stochastic framework of neurogenesis
underlies the assembly of neocortical cytoarchitecture. eLife. 2019;8.
doi:10.7554/eLife.51381
apa: Llorca, A., Ciceri, G., Beattie, R. J., Wong, F. K., Diana, G., Serafeimidou-Pouliou,
E., … Marín, O. (2019). A stochastic framework of neurogenesis underlies the assembly
of neocortical cytoarchitecture. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.51381
chicago: Llorca, Alfredo, Gabriele Ciceri, Robert J Beattie, Fong Kuan Wong, Giovanni
Diana, Eleni Serafeimidou-Pouliou, Marian Fernández-Otero, et al. “A Stochastic
Framework of Neurogenesis Underlies the Assembly of Neocortical Cytoarchitecture.”
ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/eLife.51381.
ieee: A. Llorca et al., “A stochastic framework of neurogenesis underlies
the assembly of neocortical cytoarchitecture,” eLife, vol. 8. eLife Sciences
Publications, 2019.
ista: Llorca A, Ciceri G, Beattie RJ, Wong FK, Diana G, Serafeimidou-Pouliou E,
Fernández-Otero M, Streicher C, Arnold SJ, Meyer M, Hippenmeyer S, Maravall M,
Marín O. 2019. A stochastic framework of neurogenesis underlies the assembly of
neocortical cytoarchitecture. eLife. 8, e51381.
mla: Llorca, Alfredo, et al. “A Stochastic Framework of Neurogenesis Underlies the
Assembly of Neocortical Cytoarchitecture.” ELife, vol. 8, e51381, eLife
Sciences Publications, 2019, doi:10.7554/eLife.51381.
short: A. Llorca, G. Ciceri, R.J. Beattie, F.K. Wong, G. Diana, E. Serafeimidou-Pouliou,
M. Fernández-Otero, C. Streicher, S.J. Arnold, M. Meyer, S. Hippenmeyer, M. Maravall,
O. Marín, ELife 8 (2019).
date_created: 2019-12-22T23:00:42Z
date_published: 2019-11-18T00:00:00Z
date_updated: 2026-04-03T09:46:33Z
day: '18'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.7554/eLife.51381
ec_funded: 1
external_id:
isi:
- '000508156800001'
pmid:
- '31736464'
file:
- access_level: open_access
checksum: b460ecc33e1a68265e7adea775021f3a
content_type: application/pdf
creator: dernst
date_created: 2020-02-18T15:19:26Z
date_updated: 2020-07-14T12:47:53Z
file_id: '7503'
file_name: 2019_eLife_Llorca.pdf
file_size: 2960543
relation: main_file
file_date_updated: 2020-07-14T12:47:53Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: A stochastic framework of neurogenesis underlies the assembly of neocortical
cytoarchitecture
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 8
year: '2019'
...
---
_id: '8547'
abstract:
- lang: eng
text: The cerebral cortex contains multiple hierarchically organized areas with
distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying
the emergence of this diversity remain unclear. Here, we have quantitatively investigated
the neuronal output of individual progenitor cells in the ventricular zone of
the developing mouse neocortex using a combination of methods that together circumvent
the biases and limitations of individual approaches. We found that individual
cortical progenitor cells show a high degree of stochasticity and generate pyramidal
cell lineages that adopt a wide range of laminar configurations. Mathematical
modelling these lineage data suggests that a small number of progenitor cell populations,
each generating pyramidal cells following different stochastic developmental programs,
suffice to generate the heterogenous complement of pyramidal cell lineages that
collectively build the complex cytoarchitecture of the neocortex.
acknowledgement: We thank I. Andrew and S.E. Bae for excellent technical assistance,
F. Gage for plasmids, and K. Nave (Nex-Cre) for mouse colonies. We thank members
of the Marín and Rico laboratories for stimulating discussions and ideas. Our research
on this topic is supported by grants from the European Research Council (ERC-2017-AdG
787355 to O.M and ERC2016-CoG 725780 to S.H.) and Wellcome Trust (103714MA) to O.M.
L.L. was the recipient of an EMBO long-term postdoctoral fellowship, R.B. received
support from FWF Lise-Meitner program (M 2416) and F.K.W. was supported by an EMBO
postdoctoral fellowship and is currently a Marie Skłodowska-Curie Fellow from the
European Commission under the H2020 Programme.
article_processing_charge: No
author:
- first_name: Alfredo
full_name: Llorca, Alfredo
last_name: Llorca
- first_name: Gabriele
full_name: Ciceri, Gabriele
last_name: Ciceri
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Fong K.
full_name: Wong, Fong K.
last_name: Wong
- first_name: Giovanni
full_name: Diana, Giovanni
last_name: Diana
- first_name: Eleni
full_name: Serafeimidou, Eleni
last_name: Serafeimidou
- first_name: Marian
full_name: Fernández-Otero, Marian
last_name: Fernández-Otero
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Sebastian J.
full_name: Arnold, Sebastian J.
last_name: Arnold
- first_name: Martin
full_name: Meyer, Martin
last_name: Meyer
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Miguel
full_name: Maravall, Miguel
last_name: Maravall
- first_name: Oscar
full_name: Marín, Oscar
last_name: Marín
citation:
ama: Llorca A, Ciceri G, Beattie RJ, et al. Heterogeneous progenitor cell behaviors
underlie the assembly of neocortical cytoarchitecture. bioRxiv. doi:10.1101/494088
apa: Llorca, A., Ciceri, G., Beattie, R. J., Wong, F. K., Diana, G., Serafeimidou,
E., … Marín, O. (n.d.). Heterogeneous progenitor cell behaviors underlie the assembly
of neocortical cytoarchitecture. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/494088
chicago: Llorca, Alfredo, Gabriele Ciceri, Robert J Beattie, Fong K. Wong, Giovanni
Diana, Eleni Serafeimidou, Marian Fernández-Otero, et al. “Heterogeneous Progenitor
Cell Behaviors Underlie the Assembly of Neocortical Cytoarchitecture.” BioRxiv.
Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/494088.
ieee: A. Llorca et al., “Heterogeneous progenitor cell behaviors underlie
the assembly of neocortical cytoarchitecture,” bioRxiv. Cold Spring Harbor
Laboratory.
ista: Llorca A, Ciceri G, Beattie RJ, Wong FK, Diana G, Serafeimidou E, Fernández-Otero
M, Streicher C, Arnold SJ, Meyer M, Hippenmeyer S, Maravall M, Marín O. Heterogeneous
progenitor cell behaviors underlie the assembly of neocortical cytoarchitecture.
bioRxiv, 10.1101/494088.
mla: Llorca, Alfredo, et al. “Heterogeneous Progenitor Cell Behaviors Underlie the
Assembly of Neocortical Cytoarchitecture.” BioRxiv, Cold Spring Harbor
Laboratory, doi:10.1101/494088.
short: A. Llorca, G. Ciceri, R.J. Beattie, F.K. Wong, G. Diana, E. Serafeimidou,
M. Fernández-Otero, C. Streicher, S.J. Arnold, M. Meyer, S. Hippenmeyer, M. Maravall,
O. Marín, BioRxiv (n.d.).
date_created: 2020-09-21T12:01:50Z
date_published: 2018-12-13T00:00:00Z
date_updated: 2024-10-22T10:46:39Z
day: '13'
department:
- _id: SiHi
doi: 10.1101/494088
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/494088
month: '12'
oa: 1
oa_version: Preprint
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
status: public
title: Heterogeneous progenitor cell behaviors underlie the assembly of neocortical
cytoarchitecture
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2018'
...