Biopolym. Cell. 2019; 35(3):205-206.
Хроніка та інформація
Nuclear function of vinculin in mouse primary oocytes
- Laboratory of Epigenetics of the Cell Nucleus, Institute of Molecular Genetics AS CR, division BIOCEV
Vestec, Czech Republic - Laboratory of the Biology of the Cell Nucleus, Institute of Molecular Genetics AS CR
Prague, Czech Republic
Abstract
Meiosis is a key process of sexual reproducing organisms and contributes to their genetic variability. The identification of new players affecting meiosis during gametogenesis could lead to revelation of new functions of chromosomal dynamics and to identification of some possible complications during meiosis that remain unexplained. It has been shown that inaccuracies during the meiotic phases result in the chromosomal aberrations and nondisjunctions, that underlie various human genetic disorders (Down's syndrome, Klinefelter's syndrome, Turner's syndrome) or lead to infertility (up to 15% of the human population). Our project focuses on the dynamics of chromosomes during gametogenesis in the eukaryotic model M. musculus, especially on the role of vinculin (VCL) in the nucleus of mouse meiocytes. VCL is known as a cytoplasmic actin-binding protein associated with cell-cell and cell-matrix junctions. However, we observed a localization of VCL to the nuclei of primary spermatocytes in prophase I. The depletion of VCL in the primary spermatocytes has an effect of reduced fertility, premature desynapsis of homologous chromosomes in the diplotene stage and VCL also showed to be important for the exit from diplotene stage of meiosis I. My part of the project is to study VCL in primary oocytes. My aim is to answer the questions: what is the localization of VCL in prophase I oocytes? Is the involvement of VCL in prophase I oocytes similar as we observe in spermatocytes? What is the effect of VCL depletion on the progression of meiosis I in oogenesis? Are there any chromosomal aberrations? What is the fertility of these VCL-deficient females? Main methods I am using to answer these questions are: crossing mice to generate a conditional VCL knock-out in mouse ovaries using the Cre lox-P system; isolation of embryonic ovaries in 15-18 dpc; phenotyping the mature ovaries of adult mice. So far, we confirmed a reduced fertility of VCL cKO females, specifically a significantly lower number of pups. Thus, we plan an in vitro fertilization assay to specify the fertility phenotype. Next, we observed a co-localization of VCL with the synaptonemal complex so we want to study the assembly and disassembly process of synaptonemal complex after depletion of VCL in primary oocytes. Acknowledgement: Supported by the project „BIOCEV” (CZ.1.05/1.1.00/02.0109) and "Modernization and support of research activities of the national infrastructure for biological and medical imaging Czech-BioImaging" (No. CZ.02.1.01/0.0/0.0/16_013/0001775) funded by the European Regional Development Fund, by GACR (16-03403S and 18-19714S) and UMG/RVO: 68378050. We acknowledge the Ministry of Education, Youth and Sports of Czech Republic COST Inter-excellence internship program LTC17.
Повний текст: (PDF, англійською)