Institutional creator:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Contributor:

Kalita-Bykowska, Katarzyna (1974– ) : Supervisor ; Liszewska, Ewa : Auxiliary supervisor

Publisher:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Place of publishing:

Warszawa

Description:

142 pages : illustrations ; 30 cm ; Bibliography ; Summary in English

Degree name:

PhD in Biological Sciences

Degree discipline :

Biological Sciences

Degree grantor:

Nencki Institute of Experimental Biology PAS ; degree obtained: 28.06.2024

Type of object:

Thesis

Abstract:

Serum Response Factor (SRF) is a key transcription factor that regulates gene expression in the adult brain in response to neuronal stimulation. Recent findings reveal the role of SRF and MKL in prenatal neuronal cell development. Despite this knowledge, the role of SRF and MKL in postnatal neuronal development remains poorly understood. Studies indicate a link between single nucleotide changes (SNP) in MKL1/2 an elevated risk of neurodevelopmental diseases associated with abnormalities in the process of neuronal maturation. The influence of SRF and MKL on development of dendritic trees and spines in neurons is still poorly studied. The results presented in this thesis show that deletion of the SRF during early postnatal development in vitro decreases the number and total length of dendrites and reduces dendritic tree complexity. Neurons lacking SRF also exhibit a lower density of dendritic spines and an increased number of immature spines. Additionally, the study investigated the influence of SNP in MKL, identified in humans, on their protein function in neurons in vitro. The subcellular localization of the proteins, their ability to activate transcription, and their effect on dendritic tree maturation were analyzed. Results demonstrate that overexpression of MKLs, influenced by BDNF, alters their neuronal localization, activates SRF-dependent transcription, and increases the complexity of the dendritic tree in vitro. Moreover, we identified SNP in MKL1/2 that disrupted their function. The study was extended with the analysis of the development of human neuronal cells obtained by differentiation from induced pluripotent stem cells. Neurons arising from neural stem cells where SRF was silenced using shRNA exhibited an increase in the number of basal dendrites. In conclusion, the downregulation of the SRF and SNP in MKL contributes to abnormalities in the neuronal structure during development in vitro. These morphological changes are often observed in animal models of neurodevelopmental diseases.

Detailed Resource Type:

PhD Dissertations

Resource Identifier:

oai:rcin.org.pl:241446

Source:

IBD PAN, call no. 20340

Language:

pol

Language of abstract:

eng

Rights:

Rights Reserved - Free Access

Terms of use:

Copyright-protected material. May be used within the limits of statutory user freedoms

Copyright holder:

Publication made available with the written permission of the author

Digitizing institution:

Nencki Institute of Experimental Biology of the Polish Academy of Sciences

Original in:

Library of the Nencki Institute of Experimental Biology PAS

Access:

Open