Analysing the Role of CYFIP1 for Mouse Central Nervous System Development Using a Conditional Knockout System
Analysing the Role of CYFIP1 for Mouse Central Nervous System Development Using a Conditional Knockout System
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DissertationDate of Exam
21.08.2023Date of Publication
09.10.2023Advisor
Witke, WalterCo-Referee
Blaess, SandraMetadata
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Abstract
The development of the central nervous system (CNS) is a tightly spatiotemporal-regulated process with critical morphogenetic changes, each involving cytoskeletal dynamics. Tight regulation of actin polymerisation, depolymerisation and branching is essential for maintaining cell morphology and polarity, for cell motility, as well as cell division.
Actin filaments are polymerised de novo from an actin nucleus. One central actin nucleation promoting factor is the canonical WAVE regulatory complex (WRC), a pentameric protein complex which comprises CYFIP1 (cytoplasmic fragile-X mental retardation protein interacting protein 1) as a crucial regulatory subunit. CYFIP1 is regulated by the small GTPase RAC1 in controlling de novo actin polymerisation and actin filament branching.
In this thesis, studies on a mouse model are presented, where Cyfip1 was conditionally knocked out (cKO) in all neuronal precursor cells during early embryonic development. The Cyfip1;Nestin-Cre model was used to address the question of CYFIP1 function for mouse CNS development.
Cyfip1 cKO mice displayed delayed development of the cerebellum and cerebellar hypoplasia. Cyfip1 deletion resulted in ectopic positioning and clustering of major cerebellar cells, such as granule cells, Purkinje cells and Bergmann glia. Interestingly, the morphogenetic defects in Cyfip1 cKO mice were mostly restricted to the cerebellum. Data on CYFIP1-dependent aspects of cerebellar morphogenesis show how CYFIP1-dependent cell dynamics participate in morphogenetic events. This work on CYFIP1 helps to unravel the mechanisms by which actin dynamics contribute to brain development.
Actin filaments are polymerised de novo from an actin nucleus. One central actin nucleation promoting factor is the canonical WAVE regulatory complex (WRC), a pentameric protein complex which comprises CYFIP1 (cytoplasmic fragile-X mental retardation protein interacting protein 1) as a crucial regulatory subunit. CYFIP1 is regulated by the small GTPase RAC1 in controlling de novo actin polymerisation and actin filament branching.
In this thesis, studies on a mouse model are presented, where Cyfip1 was conditionally knocked out (cKO) in all neuronal precursor cells during early embryonic development. The Cyfip1;Nestin-Cre model was used to address the question of CYFIP1 function for mouse CNS development.
Cyfip1 cKO mice displayed delayed development of the cerebellum and cerebellar hypoplasia. Cyfip1 deletion resulted in ectopic positioning and clustering of major cerebellar cells, such as granule cells, Purkinje cells and Bergmann glia. Interestingly, the morphogenetic defects in Cyfip1 cKO mice were mostly restricted to the cerebellum. Data on CYFIP1-dependent aspects of cerebellar morphogenesis show how CYFIP1-dependent cell dynamics participate in morphogenetic events. This work on CYFIP1 helps to unravel the mechanisms by which actin dynamics contribute to brain development.
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570 Biowissenschaften, BiologieBeuck, Carina Alexandra: Analysing the Role of CYFIP1 for Mouse Central Nervous System Development Using a Conditional Knockout System. - Bonn, 2023. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-72266
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-72266
@phdthesis{handle:20.500.11811/11089,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-72266,
author = {{Carina Alexandra Beuck}},
title = {Analysing the Role of CYFIP1 for Mouse Central Nervous System Development Using a Conditional Knockout System},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2023,
month = oct,
note = {The development of the central nervous system (CNS) is a tightly spatiotemporal-regulated process with critical morphogenetic changes, each involving cytoskeletal dynamics. Tight regulation of actin polymerisation, depolymerisation and branching is essential for maintaining cell morphology and polarity, for cell motility, as well as cell division.
Actin filaments are polymerised de novo from an actin nucleus. One central actin nucleation promoting factor is the canonical WAVE regulatory complex (WRC), a pentameric protein complex which comprises CYFIP1 (cytoplasmic fragile-X mental retardation protein interacting protein 1) as a crucial regulatory subunit. CYFIP1 is regulated by the small GTPase RAC1 in controlling de novo actin polymerisation and actin filament branching.
In this thesis, studies on a mouse model are presented, where Cyfip1 was conditionally knocked out (cKO) in all neuronal precursor cells during early embryonic development. The Cyfip1;Nestin-Cre model was used to address the question of CYFIP1 function for mouse CNS development.
Cyfip1 cKO mice displayed delayed development of the cerebellum and cerebellar hypoplasia. Cyfip1 deletion resulted in ectopic positioning and clustering of major cerebellar cells, such as granule cells, Purkinje cells and Bergmann glia. Interestingly, the morphogenetic defects in Cyfip1 cKO mice were mostly restricted to the cerebellum. Data on CYFIP1-dependent aspects of cerebellar morphogenesis show how CYFIP1-dependent cell dynamics participate in morphogenetic events. This work on CYFIP1 helps to unravel the mechanisms by which actin dynamics contribute to brain development.},
url = {https://hdl.handle.net/20.500.11811/11089}
}
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-72266,
author = {{Carina Alexandra Beuck}},
title = {Analysing the Role of CYFIP1 for Mouse Central Nervous System Development Using a Conditional Knockout System},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2023,
month = oct,
note = {The development of the central nervous system (CNS) is a tightly spatiotemporal-regulated process with critical morphogenetic changes, each involving cytoskeletal dynamics. Tight regulation of actin polymerisation, depolymerisation and branching is essential for maintaining cell morphology and polarity, for cell motility, as well as cell division.
Actin filaments are polymerised de novo from an actin nucleus. One central actin nucleation promoting factor is the canonical WAVE regulatory complex (WRC), a pentameric protein complex which comprises CYFIP1 (cytoplasmic fragile-X mental retardation protein interacting protein 1) as a crucial regulatory subunit. CYFIP1 is regulated by the small GTPase RAC1 in controlling de novo actin polymerisation and actin filament branching.
In this thesis, studies on a mouse model are presented, where Cyfip1 was conditionally knocked out (cKO) in all neuronal precursor cells during early embryonic development. The Cyfip1;Nestin-Cre model was used to address the question of CYFIP1 function for mouse CNS development.
Cyfip1 cKO mice displayed delayed development of the cerebellum and cerebellar hypoplasia. Cyfip1 deletion resulted in ectopic positioning and clustering of major cerebellar cells, such as granule cells, Purkinje cells and Bergmann glia. Interestingly, the morphogenetic defects in Cyfip1 cKO mice were mostly restricted to the cerebellum. Data on CYFIP1-dependent aspects of cerebellar morphogenesis show how CYFIP1-dependent cell dynamics participate in morphogenetic events. This work on CYFIP1 helps to unravel the mechanisms by which actin dynamics contribute to brain development.},
url = {https://hdl.handle.net/20.500.11811/11089}
}
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