Christer Höög's Group
By describing the function of a protein structure called the synaptonemal complex in germ cells, we hope to get a better understanding of the defective cellular mechanisms that give rise to human eggs with too few or too many chromosomes. The results should contribute to the development of more effective methods for in vitro fertilization.
Meiosis is a specialized cell division process that is active in germ cells. During meiosis, genetically distinct haploid cells are generated through a process that involves one DNA replication step followed by two cell divisions. Meiosis in human female germ cells is highly error-prone and frequently give rise to gametes that have too many or too few chromosomes (aneuploid cells). Aneuploidy is the most common chromosome abnormality in humans and clinically very important, being the leading genetic cause of miscarriage, congenital birth defects and mental retardation.
The focus of the research in the laboratory is to understand the role of the synaptonemal complex. The synaptonemal complex is an evolutionary conserved meiosis-specific protein complex that ensures the fidelity of the chromosome segregation process in germ cells. Despite the central biological role of the synaptonemal complex in meiotic chromosome architecture, our knowledge of the function of this protein complex is yet limited.
To unravel the function of the synaptonemal complex, we are analyzing this structure by a combination of genetic, biochemical and ultrastructural approaches. Inactivation of one of the components of the synaptonemal complex (Sycp3) in mice replicates many of the chromosomal segregation deficiencies known to occur during meiosis in human oocytes. The ongoing studies of the synaptonemal complex will provide us with a more comprehensive view of the molecular pathways that contribute to aneuploidy in female germ cells and also support the development of more effective human assisted reproductive methods.
Sexual dimorphism in the width of the mouse synaptonemal complex.
Agostinho A, Kouznetsova A, Hernández-Hernández A, Bernhem K, Blom H, Brismar H, et al
J. Cell. Sci. 2018 03;131(5):
CTCF contributes in a critical way to spermatogenesis and male fertility.
Hernández-Hernández A, Lilienthal I, Fukuda N, Galjart N, Höög C
Sci Rep 2016 06;6():28355
The central element of the synaptonemal complex in mice is organized as a bilayered junction structure.
Hernández-Hernández A, Masich S, Fukuda T, Kouznetsova A, Sandin S, Daneholt B, et al
J. Cell. Sci. 2016 06;129(11):2239-49
High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation.
Agostinho A, Manneberg O, van Schendel R, Hernández-Hernández A, Kouznetsova A, Blom H, et al
EMBO Rep. 2016 06;17(6):901-13
Merotelic attachments allow alignment and stabilization of chromatids in meiosis II oocytes.
Kouznetsova A, Hernández-Hernández A, Höög C
Nat Commun 2014 Jul;5():4409