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Beta-actin as a regulator of crucial developmental processes: focus on a nuclear role for beta-actin

Davina Tondeleir UGent (2013)
abstract
In mammals the actin family consists of 6 isoforms, and although the roles of actin isforms have been rigorously studied in adult life, the functions of actin family members during development are poorly understood. Especially the emerging role of beta-actin in the nucleus remains enigmatic. To investigate the role of beta-actin in mammalian development, a beta-actin knockout mouse model was used. Homozygous beta-actin knockout mice are lethal at embryonic day (E)10.5. At E10.25 beta-actin knockout embryos are growth retarded and display a pale yolk sac and embryo proper that is suggestive of altered erythropoiesis. Using a combined strategy involving bioinformatics, biochemical, and novel genetic rescue approaches, we report that lack of beta-actin resulted in a block of primitive and definitive hematopoiesis. Reduced levels of the transcription factor Gata2 were associated with this phenotype. Consistent with this, ChIP analysis revealed multiple binding sites for beta-actin in the Gata2 promoter. Gata2 mRNA levels could almost completely be restored by expression of an erythroid lineage restricted ROSA26-promotor based GATA2 transgene. As a result, erythroid differentiation was restored and the knockout embryos showed a significant improvement of their vascularization pattern. We here provide evidence for an association of betaactin with a developmentally important gene, Gata2. We define beta-actin as a novel modulator of Gata2 levels during early mammalian hematopoiesis. We thereby contribute to the unraveling of beta-actin’s specific nuclear functions as well as providing new molecular insights for a novel and essential function of beta-actin in embryonic development.
Please use this url to cite or link to this publication:
author
promoter
UGent
organization
year
type
dissertation
publication status
published
subject
pages
216 pages
publisher
Ghent University. Faculty of Medicine and Health Sciences
place of publication
Ghent, Belgium
defense location
Gent : Rommelaere Instituut (aud. 1.39)
defense date
2013-03-29 17:00
language
English
UGent publication?
yes
classification
D1
additional info
dissertation contains copyrighted material
copyright statement
I have transferred the copyright for this publication to the publisher
id
3192151
handle
http://hdl.handle.net/1854/LU-3192151
date created
2013-04-12 08:03:15
date last changed
2017-01-16 10:41:27
@phdthesis{3192151,
  abstract     = {In mammals the actin family consists of 6 isoforms, and although the roles of actin isforms have been rigorously studied in adult life, the functions of actin family members during development are poorly understood. Especially the emerging role of beta-actin in the nucleus remains enigmatic. To investigate the role of beta-actin in mammalian development, a beta-actin knockout mouse model was used. Homozygous beta-actin knockout mice are lethal at embryonic day (E)10.5. At E10.25 beta-actin knockout embryos are growth retarded and display a pale yolk sac and embryo proper that is suggestive of altered erythropoiesis. Using a combined strategy involving bioinformatics, biochemical, and novel genetic rescue approaches, we report that lack of beta-actin resulted in a block of primitive and definitive hematopoiesis. Reduced levels of the transcription factor Gata2 were associated with this phenotype. Consistent with this, ChIP analysis revealed multiple binding sites for beta-actin in the Gata2 promoter. Gata2 mRNA levels could almost completely be restored by expression of an erythroid lineage restricted ROSA26-promotor based GATA2 transgene. As a result, erythroid differentiation was restored and the knockout embryos showed a significant improvement of their vascularization pattern. We here provide evidence for an association of betaactin with a developmentally important gene, Gata2. We define beta-actin as a novel modulator of Gata2 levels during early mammalian hematopoiesis. We thereby contribute to the unraveling of beta-actin{\textquoteright}s specific nuclear functions as well as providing new molecular insights for a novel and essential function of beta-actin in embryonic development.},
  author       = {Tondeleir, Davina},
  language     = {eng},
  pages        = {216},
  publisher    = {Ghent University. Faculty of Medicine and Health Sciences},
  school       = {Ghent University},
  title        = {Beta-actin as a regulator of crucial developmental processes: focus on a nuclear role for beta-actin},
  year         = {2013},
}

Chicago
Tondeleir, Davina. 2013. “Beta-actin as a Regulator of Crucial Developmental Processes: Focus on a Nuclear Role for Beta-actin”. Ghent, Belgium: Ghent University. Faculty of Medicine and Health Sciences.
APA
Tondeleir, D. (2013). Beta-actin as a regulator of crucial developmental processes: focus on a nuclear role for beta-actin. Ghent University. Faculty of Medicine and Health Sciences, Ghent, Belgium.
Vancouver
1.
Tondeleir D. Beta-actin as a regulator of crucial developmental processes: focus on a nuclear role for beta-actin. [Ghent, Belgium]: Ghent University. Faculty of Medicine and Health Sciences; 2013.
MLA
Tondeleir, Davina. “Beta-actin as a Regulator of Crucial Developmental Processes: Focus on a Nuclear Role for Beta-actin.” 2013 : n. pag. Print.