---
_id: '14058'
abstract:
- lang: eng
text: "Females and males across species are subject to divergent selective pressures
arising\r\nfrom di↵erent reproductive interests and ecological niches. This often
translates into a\r\nintricate array of sex-specific natural and sexual selection
on traits that have a shared\r\ngenetic basis between both sexes, causing a genetic
sexual conflict. The resolution of\r\nthis conflict mostly relies on the evolution
of sex-specific expression of the shared genes,\r\nleading to phenotypic sexual
dimorphism. Such sex-specific gene expression is thought\r\nto evolve via modifications
of the genetic networks ultimately linked to sex-determining\r\ntranscription
factors. Although much empirical and theoretical evidence supports this\r\nstandard
picture of the molecular basis of sexual conflict resolution, there still are
a\r\nfew open questions regarding the complex array of selective forces driving
phenotypic\r\ndi↵erentiation between the sexes, as well as the molecular mechanisms
underlying sexspecific adaptation. I address some of these open questions in my
PhD thesis.\r\nFirst, how do patterns of phenotypic sexual dimorphism vary within
populations,\r\nas a response to the temporal and spatial changes in sex-specific
selective forces? To\r\ntackle this question, I analyze the patterns of sex-specific
phenotypic variation along\r\nthree life stages and across populations spanning
the whole geographical range of Rumex\r\nhastatulus, a wind-pollinated angiosperm,
in the first Chapter of the thesis.\r\nSecond, how do gene expression patterns
lead to phenotypic dimorphism, and what\r\nare the molecular mechanisms underlying
the observed transcriptomic variation? I\r\naddress this question by examining
the sex- and tissue-specific expression variation in\r\nnewly-generated datasets
of sex-specific expression in heads and gonads of Drosophila\r\nmelanogaster.
I additionally used two complementary approaches for the study of the\r\ngenetic
basis of sex di↵erences in gene expression in the second and third Chapters of\r\nthe
thesis.\r\nThird, how does intersex correlation, thought to be one of the main
aspects constraining the ability for the two sexes to decouple, interact with
the evolution of sexual\r\ndimorphism? I develop models of sex-specific stabilizing
selection, mutation and drift\r\nto formalize common intuition regarding the patterns
of covariation between intersex\r\ncorrelation and sexual dimorphism in the fourth
Chapter of the thesis.\r\nAlltogether, the work described in this PhD thesis provides
useful insights into the\r\nlinks between genetic, transcriptomic and phenotypic
layers of sex-specific variation,\r\nand contributes to our general understanding
of the dynamics of sexual dimorphism\r\nevolution."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Gemma
full_name: Puixeu Sala, Gemma
id: 33AB266C-F248-11E8-B48F-1D18A9856A87
last_name: Puixeu Sala
orcid: 0000-0001-8330-1754
citation:
ama: 'Puixeu Sala G. The molecular basis of sexual dimorphism: Experimental and
theoretical characterization of phenotypic, transcriptomic and genetic patterns
of sex-specific adaptation. 2023. doi:10.15479/at:ista:14058'
apa: 'Puixeu Sala, G. (2023). The molecular basis of sexual dimorphism: Experimental
and theoretical characterization of phenotypic, transcriptomic and genetic patterns
of sex-specific adaptation. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:14058'
chicago: 'Puixeu Sala, Gemma. “The Molecular Basis of Sexual Dimorphism: Experimental
and Theoretical Characterization of Phenotypic, Transcriptomic and Genetic Patterns
of Sex-Specific Adaptation.” Institute of Science and Technology Austria, 2023.
https://doi.org/10.15479/at:ista:14058.'
ieee: 'G. Puixeu Sala, “The molecular basis of sexual dimorphism: Experimental and
theoretical characterization of phenotypic, transcriptomic and genetic patterns
of sex-specific adaptation,” Institute of Science and Technology Austria, 2023.'
ista: 'Puixeu Sala G. 2023. The molecular basis of sexual dimorphism: Experimental
and theoretical characterization of phenotypic, transcriptomic and genetic patterns
of sex-specific adaptation. Institute of Science and Technology Austria.'
mla: 'Puixeu Sala, Gemma. The Molecular Basis of Sexual Dimorphism: Experimental
and Theoretical Characterization of Phenotypic, Transcriptomic and Genetic Patterns
of Sex-Specific Adaptation. Institute of Science and Technology Austria, 2023,
doi:10.15479/at:ista:14058.'
short: 'G. Puixeu Sala, The Molecular Basis of Sexual Dimorphism: Experimental and
Theoretical Characterization of Phenotypic, Transcriptomic and Genetic Patterns
of Sex-Specific Adaptation, Institute of Science and Technology Austria, 2023.'
date_created: 2023-08-15T10:20:40Z
date_published: 2023-08-15T00:00:00Z
date_updated: 2023-12-13T12:15:36Z
day: '15'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: GradSch
- _id: NiBa
- _id: BeVi
doi: 10.15479/at:ista:14058
ec_funded: 1
file:
- access_level: closed
checksum: 4e44e169f2724ee8c9324cd60bcc2b71
content_type: application/zip
creator: gpuixeus
date_created: 2023-08-16T18:15:17Z
date_updated: 2023-08-17T06:55:24Z
file_id: '14075'
file_name: Thesis_latex_forpdfa.zip
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creator: gpuixeus
date_created: 2023-08-18T10:47:55Z
date_updated: 2023-08-18T10:47:55Z
file_id: '14079'
file_name: PhDThesis_PuixeuG.pdf
file_size: 19856686
relation: main_file
success: 1
file_date_updated: 2023-08-18T10:47:55Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '08'
oa: 1
oa_version: Published Version
page: '230'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 9B9DFC9E-BA93-11EA-9121-9846C619BF3A
grant_number: '25817'
name: 'Sexual conflict: resolution, constraints and biomedical implications'
publication_identifier:
isbn:
- 978-3-99078-035-0
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '9803'
relation: research_data
status: public
- id: '12933'
relation: research_data
status: public
- id: '6831'
relation: part_of_dissertation
status: public
- id: '14077'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Beatriz
full_name: Vicoso, Beatriz
id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
last_name: Vicoso
orcid: 0000-0002-4579-8306
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
title: 'The molecular basis of sexual dimorphism: Experimental and theoretical characterization
of phenotypic, transcriptomic and genetic patterns of sex-specific adaptation'
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: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '10'
abstract:
- lang: eng
text: Genomic imprinting is an epigenetic process that leads to parent of origin-specific
gene expression in a subset of genes. Imprinted genes are essential for brain
development, and deregulation of imprinting is associated with neurodevelopmental
diseases and the pathogenesis of psychiatric disorders. However, the cell-type
specificity of imprinting at single cell resolution, and how imprinting and thus
gene dosage regulates neuronal circuit assembly is still largely unknown. Here,
MADM (Mosaic Analysis with Double Markers) technology was employed to assess genomic
imprinting at single cell level. By visualizing MADM-induced uniparental disomies
(UPDs) in distinct colors at single cell level in genetic mosaic animals, this
experimental paradigm provides a unique quantitative platform to systematically
assay the UPD-mediated imbalances in imprinted gene expression at unprecedented
resolution. An experimental pipeline based on FACS, RNA-seq and bioinformatics
analysis was established and applied to systematically map cell-type-specific
‘imprintomes’ in the mouse brain. The results revealed that parental-specific
expression of imprinted genes per se is rarely cell-type-specific even at the
individual cell level. Conversely, when we extended the comparison to downstream
responses resulting from imbalanced imprinted gene expression, we discovered an
unexpectedly high degree of cell-type specificity. Furthermore, we determined
a novel function of genomic imprinting in cortical astrocyte production and in
olfactory bulb (OB) granule cell generation. These results suggest important functional
implication of genomic imprinting for generating cell-type diversity in the brain.
In addition, MADM provides a powerful tool to study candidate genes by concomitant
genetic manipulation and fluorescent labelling of single cells. MADM-based candidate
gene approach was utilized to identify potential imprinted genes involved in the
generation of cortical astrocytes and OB granule cells. We investigated p57Kip2,
a maternally expressed gene and known cell cycle regulator. Although we found
that p57Kip2 does not play a role in these processes, we detected an unexpected
function of the paternal allele previously thought to be silent. Finally, we took
advantage of a key property of MADM which is to allow unambiguous investigation
of environmental impact on single cells. The experimental pipeline based on FACS
and RNA-seq analysis of MADM-labeled cells was established to probe the functional
differences of single cell loss of gene function compared to global loss of function
on a transcriptional level. With this method, both common and distinct responses
were isolated due to cell-autonomous and non-autonomous effects acting on genotypically
identical cells. As a result, transcriptional changes were identified which result
solely from the surrounding environment. Using the MADM technology to study genomic
imprinting at single cell resolution, we have identified cell-type-specific gene
expression, novel gene function and the impact of environment on single cell transcriptomes.
Together, these provide important insights to the understanding of mechanisms
regulating cell-type specificity and thus diversity in the brain.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
citation:
ama: Laukoter S. Role of genomic imprinting in cerebral cortex development. 2018:1-139.
doi:10.15479/AT:ISTA:th1057
apa: Laukoter, S. (2018). Role of genomic imprinting in cerebral cortex development.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th1057
chicago: Laukoter, Susanne. “Role of Genomic Imprinting in Cerebral Cortex Development.”
Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th1057.
ieee: S. Laukoter, “Role of genomic imprinting in cerebral cortex development,”
Institute of Science and Technology Austria, 2018.
ista: Laukoter S. 2018. Role of genomic imprinting in cerebral cortex development.
Institute of Science and Technology Austria.
mla: Laukoter, Susanne. Role of Genomic Imprinting in Cerebral Cortex Development.
Institute of Science and Technology Austria, 2018, pp. 1–139, doi:10.15479/AT:ISTA:th1057.
short: S. Laukoter, Role of Genomic Imprinting in Cerebral Cortex Development, Institute
of Science and Technology Austria, 2018.
date_created: 2018-12-11T11:44:08Z
date_published: 2018-11-21T00:00:00Z
date_updated: 2023-09-07T12:40:44Z
day: '21'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: SiHi
doi: 10.15479/AT:ISTA:th1057
file:
- access_level: closed
checksum: 41fdbf5fdce312802935d88a8ad9932c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: dernst
date_created: 2019-05-10T07:47:04Z
date_updated: 2019-11-23T23:30:03Z
embargo_to: open_access
file_id: '6396'
file_name: Thesis_LaukoterSusanne_FINAL.docx
file_size: 17949175
relation: source_file
- access_level: open_access
checksum: 53001a9a0c9e570e598d861bb0af28aa
content_type: application/pdf
creator: dernst
date_created: 2019-05-10T07:47:04Z
date_updated: 2021-02-11T11:17:16Z
embargo: 2019-11-21
file_id: '6397'
file_name: Thesis_LaukoterSusanne_FINAL.pdf
file_size: 21187245
relation: main_file
file_date_updated: 2021-02-11T11:17:16Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: 1 - 139
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '8046'
pubrep_id: '1057'
status: public
supervisor:
- first_name: Beatriz
full_name: Vicoso, Beatriz
id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
last_name: Vicoso
orcid: 0000-0002-4579-8306
title: Role of genomic imprinting in cerebral cortex development
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2018'
...