---
_id: '9962'
abstract:
- lang: eng
text: The brain is one of the largest and most complex organs and it is composed
of billions of neurons that communicate together enabling e.g. consciousness.
The cerebral cortex is the largest site of neural integration in the central nervous
system. Concerted radial migration of newly born cortical projection neurons,
from their birthplace to their final position, is a key step in the assembly of
the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal
migration in vivo are however still unclear. Recent evidence suggests that distinct
signaling cues act cell-autonomously but differentially at certain steps during
the overall migration process. Moreover, functional analysis of genetic mosaics
(mutant neurons present in wild-type/heterozygote environment) using the MADM
(Mosaic Analysis with Double Markers) analyses in comparison to global knockout
also indicate a significant degree of non-cell-autonomous and/or community effects
in the control of cortical neuron migration. The interactions of cell-intrinsic
(cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely
unknown. In part of this thesis work we established a MADM-based experimental
strategy for the quantitative analysis of cell-autonomous gene function versus
non-cell-autonomous and/or community effects. The direct comparison of mutant
neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional
and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively
analyze non-cell-autonomous effects. Such analysis enable the high-resolution
analysis of projection neuron migration dynamics in distinct environments with
concomitant isolation of genomic and proteomic profiles. Using these experimental
paradigms and in combination with computational modeling we show and characterize
the nature of non-cell-autonomous effects to coordinate radial neuron migration.
Furthermore, this thesis discusses recent developments in neurodevelopment with
focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal
migration.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
citation:
ama: Hansen AH. Cell-autonomous gene function and non-cell-autonomous effects in
radial projection neuron migration. 2021. doi:10.15479/at:ista:9962
apa: Hansen, A. H. (2021). Cell-autonomous gene function and non-cell-autonomous
effects in radial projection neuron migration. Institute of Science and Technology
Austria. https://doi.org/10.15479/at:ista:9962
chicago: Hansen, Andi H. “Cell-Autonomous Gene Function and Non-Cell-Autonomous
Effects in Radial Projection Neuron Migration.” Institute of Science and Technology
Austria, 2021. https://doi.org/10.15479/at:ista:9962.
ieee: A. H. Hansen, “Cell-autonomous gene function and non-cell-autonomous effects
in radial projection neuron migration,” Institute of Science and Technology Austria,
2021.
ista: Hansen AH. 2021. Cell-autonomous gene function and non-cell-autonomous effects
in radial projection neuron migration. Institute of Science and Technology Austria.
mla: Hansen, Andi H. Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects
in Radial Projection Neuron Migration. Institute of Science and Technology
Austria, 2021, doi:10.15479/at:ista:9962.
short: A.H. Hansen, Cell-Autonomous Gene Function and Non-Cell-Autonomous Effects
in Radial Projection Neuron Migration, Institute of Science and Technology Austria,
2021.
date_created: 2021-08-29T12:36:50Z
date_published: 2021-09-02T00:00:00Z
date_updated: 2023-09-22T09:58:30Z
day: '02'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SiHi
doi: 10.15479/at:ista:9962
file:
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checksum: 66b56f5b988b233dc66a4f4b4fb2cdfe
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creator: ahansen
date_created: 2021-08-30T09:17:39Z
date_updated: 2022-09-03T22:30:04Z
embargo_to: open_access
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date_updated: 2022-09-03T22:30:04Z
embargo: 2022-09-02
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file_name: Thesis_Hansen_PDFA-1a.pdf
file_size: 13457469
relation: main_file
file_date_updated: 2022-09-03T22:30:04Z
has_accepted_license: '1'
keyword:
- Neuronal migration
- Non-cell-autonomous
- Cell-autonomous
- Neurodevelopmental disease
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '182'
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
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relation: part_of_dissertation
status: public
- id: '960'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
title: Cell-autonomous gene function and non-cell-autonomous effects in radial projection
neuron migration
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: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2021'
...
---
_id: '7902'
abstract:
- lang: eng
text: "Mosaic genetic analysis has been widely used in different model organisms
such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific
fashion. More recently, and less easily conducted, mosaic genetic analysis in
mice has also been enabled with the ambition to shed light on human gene function
and disease. These genetic tools are of particular interest, but not restricted
to, the study of the brain. Notably, the MADM technology offers a genetic approach
in mice to visualize and concomitantly manipulate small subsets of genetically
defined cells at a clonal level and single cell resolution. MADM-based analysis
has already advanced the study of genetic mechanisms regulating brain development
and is expected that further MADM-based analysis of genetic alterations will continue
to reveal important insights on the fundamental principles of development and
disease to potentially assist in the development of new therapies or treatments.\r\nIn
summary, this work completed and characterized the necessary genome-wide genetic
tools to perform MADM-based analysis at single cell level of the vast majority
of mouse genes in virtually any cell type and provided a protocol to perform lineage
tracing using the novel MADM resource. Importantly, this work also explored and
revealed novel aspects of biologically relevant events in an in vivo context,
such as the chromosome-specific bias of chromatid sister segregation pattern,
the generation of cell-type diversity in the cerebral cortex and in the cerebellum
and finally, the relevance of the interplay between the cell-autonomous gene function
and cell-non-autonomous (community) effects in radial glial progenitor lineage
progression.\r\nThis work provides a foundation and opens the door to further
elucidating the molecular mechanisms underlying neuronal diversity and astrocyte
generation."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
citation:
ama: Contreras X. Genetic dissection of neural development in health and disease
at single cell resolution. 2020. doi:10.15479/AT:ISTA:7902
apa: Contreras, X. (2020). Genetic dissection of neural development in health
and disease at single cell resolution. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:7902
chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health
and Disease at Single Cell Resolution.” Institute of Science and Technology Austria,
2020. https://doi.org/10.15479/AT:ISTA:7902.
ieee: X. Contreras, “Genetic dissection of neural development in health and disease
at single cell resolution,” Institute of Science and Technology Austria, 2020.
ista: Contreras X. 2020. Genetic dissection of neural development in health and
disease at single cell resolution. Institute of Science and Technology Austria.
mla: Contreras, Ximena. Genetic Dissection of Neural Development in Health and
Disease at Single Cell Resolution. Institute of Science and Technology Austria,
2020, doi:10.15479/AT:ISTA:7902.
short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease
at Single Cell Resolution, Institute of Science and Technology Austria, 2020.
date_created: 2020-05-29T08:27:32Z
date_published: 2020-06-05T00:00:00Z
date_updated: 2023-10-18T08:45:16Z
day: '05'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: SiHi
doi: 10.15479/AT:ISTA:7902
ec_funded: 1
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content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: xcontreras
date_created: 2020-06-05T08:18:08Z
date_updated: 2021-06-07T22:30:03Z
embargo_to: open_access
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file_name: PhDThesis_Contreras.docx
file_size: 53134142
relation: source_file
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creator: xcontreras
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date_updated: 2021-06-07T22:30:03Z
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file_name: PhDThesis_Contreras.pdf
file_size: 35117191
relation: main_file
file_date_updated: 2021-06-07T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '214'
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
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
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relation: dissertation_contains
status: public
- id: '28'
relation: dissertation_contains
status: public
- id: '7815'
relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
title: Genetic dissection of neural development in health and disease at single cell
resolution
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...