---
OA_place: publisher
_id: '20212'
abstract:
- lang: eng
text: "Cortical development has been studied for many decades and with each passing
year, we learn \r\nmore about the processes that govern the tightly regulated
developmental program. Up until \r\nrecently, the field has struggled to gain
reliable access to progenitors at the single-cell level, \r\nlimiting the resolution
at which we can study cortical development in vivo. Therefore, much of \r\nthe
data we have on mammalian cortical development is at the cell population level.
The \r\nsubsequent pages of this thesis describe novel elements of cortical development
in mice; \r\nacquired using a candidate gene approach in conjunction with Mosaic
Analysis with Double \r\nMarkers (MADM) to achieve single cell resolution. In
this thesis, I briefly provide an overview \r\nof the state of the field, describe
the methodology used to quantify morphological \r\ncharacteristics of neurons
and glia, and delve into the role of Phosphatase and tensin \r\nhomologue on chromosome
ten (Pten) in neurogenesis and gliogenesis in the developing mouse \r\ncortex.
By using MADM to generate genetic mosaics, in which only a small fraction of cells
\r\nare mutated, to study population-level changes, we can bypass the early postnatal
lethality \r\nreported in Pten conditional knockouts (cKOs) using Emx1-Cre. We
used Emx1-CreERT2 to \r\ninduce clonal deletion of Pten, and quantify RGP neurogenic
output at the single progenitor \r\nlevel. Pten-mutant neuron populations within
the mosaics were significantly expanded. In the \r\nlatter parts of this thesis,
we describe how Pten deletion leads to an increase in the abundance \r\nof astrocytes.
We availed ourselves of the flexibility offered by the MADM system to generate
\r\nPten mosaics within a series of distinct knockout tissues to test for the
interactions between \r\nPten and a battery of genes involved in distinct pro-gliogenic
signaling pathways. Our survey \r\nof Pten’s interactions with genes in key signaling
pathways reveals that ERK1/2 are the critical \r\neffectors downstream of EGFR
signaling essential for gliogenesis. Altogether, our results \r\ndemonstrate that
Pten plays critical and distinct roles throughout cortical RGP lineage \r\nprogression. "
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: "I would also like to\r\nthank the Austrian Academy of Sciences for
awarding me a 2-year DOC fellowship\r\n(DOC26253)."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
citation:
ama: Miranda O. Unraveling the role of Pten in cortical stem cell lineage progression
using MADM. 2025. doi:10.15479/AT-ISTA-20212
apa: Miranda, O. (2025). Unraveling the role of Pten in cortical stem cell lineage
progression using MADM. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20212
chicago: Miranda, Osvaldo. “Unraveling the Role of Pten in Cortical Stem Cell Lineage
Progression Using MADM.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20212.
ieee: O. Miranda, “Unraveling the role of Pten in cortical stem cell lineage progression
using MADM,” Institute of Science and Technology Austria, 2025.
ista: Miranda O. 2025. Unraveling the role of Pten in cortical stem cell lineage
progression using MADM. Institute of Science and Technology Austria.
mla: Miranda, Osvaldo. Unraveling the Role of Pten in Cortical Stem Cell Lineage
Progression Using MADM. Institute of Science and Technology Austria, 2025,
doi:10.15479/AT-ISTA-20212.
short: O. Miranda, Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression
Using MADM, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-08-22T14:07:00Z
date_published: 2025-08-22T00:00:00Z
date_updated: 2026-10-02T12:16:56Z
day: '22'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SiHi
doi: 10.15479/AT-ISTA-20212
doi_confirm: '1'
file:
- access_level: closed
checksum: 3331f76bbef74ff4908e2d2c9262045c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: omiranda
date_created: 2025-08-26T09:03:50Z
date_updated: 2026-08-26T22:30:02Z
embargo_to: open_access
file_id: '20230'
file_name: 2025_MirandaRomero_OsvaldoAntonio_Thesis.docx
file_size: 32887334
relation: source_file
- access_level: open_access
checksum: 02509d50cff8e35c5bcbf71e8d658176
content_type: application/pdf
creator: omiranda
date_created: 2025-08-26T09:05:55Z
date_updated: 2026-08-26T22:30:02Z
embargo: 2026-08-26
file_id: '20231'
file_name: 2025_MirandaRomero_OsvaldoAntonio_Thesis.pdf
file_size: 28636240
relation: main_file
file_date_updated: 2026-08-26T22:30:02Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20212
has_accepted_license: '1'
keyword:
- Pten
- mtor
- cortical development
- MADM
- Mapk
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '119'
project:
- _id: 34c9fbcb-11ca-11ed-8bc3-98fa5658610d
grant_number: '26253'
name: Molecular Mechanisms Regulating Cortical Neural Stem Cell Lineage Progression
and Astrocyte Development
publication_identifier:
isbn:
- 978-3-99078-063-3
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '17425'
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: Unraveling the role of Pten in cortical stem cell lineage progression using
MADM
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...