Genetics, Epigenetics & Gene Regulation | Molecular Cell Biology | Nucleus & Chromosome Biology
Meiosis in C. elegans
Meiosis is the specialized cell division that generates haploid germ cells, a requirement to compensate for doubling of the chromosomal content after fertilization. Meiosis also ensures genetic diversity by recombination. Defects in this process lead to unfaithful chromosome segregation and are a major cause for miscarriages and birth defects. For successful recombination in meiotic prophase, homologous chromosomes have to recognize each other, pair, and...more
Meiosis is the specialized cell division that generates haploid germ cells, a requirement to compensate for doubling of the chromosomal content after fertilization. Meiosis also ensures genetic diversity by recombination. Defects in this process lead to unfaithful chromosome segregation and are a major cause for miscarriages and birth defects. For successful recombination in meiotic prophase, homologous chromosomes have to recognize each other, pair, and finally closely associate, mediated by the synaptonemal complex, a well conserved, tripartite proteinacious structure. Interestingly, few genes and factors involved in the meiotic pairing process have been identified today. Research in my lab is therefore directed towards the identification of genes and processes essential in meiotic prophase. Special emphasis is given the study of the mechanisms of recognition and pairing of homologous chromosomes.
Excellent forward and reverse genetics and easy cytological observation of all meiotic stages make the nematode Caenorhabditis elegans an excellent model system for our studies. In forward genetic screens we have isolated numerous novel meiotic mutants that provide(d) us insight into prophase I events.
In meiotic prophase I chromosomes are moved by cytoplasmic forces transferred to the nucleus via the SUN/KASH protein module (components of the outer and inner nuclear envelope that connect chromosomes to cytoplasmatic microtubules). Abrogation of chromosome movement, as we demonstrated with the sun-1(jf18) allele, leads to precocious synapsis involving non-homologous chromosomes. We study the nature of chromosome movement and its regulation. Concomitant with chromosome movement when the SUN-1 protein redistributes into aggregates at chromosome ends, the inner nuclear envelope protein SUN-1 is reversibly modified by multiple kinases. We try to understand the contribution of the modifications to faithful chromosome segregation.
From our screen for mutants defective in meiotic prophase we succeeded in cloning the novel pairing gene, him-19. Most interestingly, with increasing age, mutant him-19 hermaphrodites display an aggravation of phenotypes. Also, in feminized him-19 worms defects are more serious while in male him-19 worms meiosis is only mildly affected. In older mutant animals presynaptic alignment and pairing are reduced and synapsis is discontinuous and non-homologous. Him-19 seems to be engaged in multiple early meiotic events. Metastructural analysis of the protein found similarities to an RNA helicase. We would like to find out what the molecular basis of the age dependent deterioration of him-19 oocytes is.
Link, Jana; Paouneskou, Dimitra; Velkova, Maria; Daryabeigi, Anahita; Laos, Triin; Labella, Sara; Barroso, Consuelo; Pacheco Piñol, Sarai; Montoya, Alex; Kramer, Holger; Woglar, Alexander; Baudrimont, Antoine; Markert, Sebastian Mathias; Stigloher, Christian; Martinez-Perez, Enrique; Dammermann, Alexander; Alsheimer, Manfred; Zetka, Monique; Jantsch, Verena (2018). Transient and Partial Nuclear Lamina Disruption Promotes Chromosome Movement in Early Meiotic Prophase. Dev Cell;45(2):212-225.e7. PMID: 29689196
Woglar, Alexander; Daryabeigi, Anahita; Adamo, Adele; Habacher, Cornelia; Machacek, Thomas; La Volpe, Adriana; Jantsch, Verena (2013). Matefin/SUN-1 Phosphorylation Is Part of a Surveillance Mechanism to Coordinate Chromosome Synapsis and Recombination with Meiotic Progression and Chromosome Movement. PLOS GENET;9(3):e1003335. PMID: 23505384
Penkner, Alexandra M; Fridkin, Alexandra; Gloggnitzer, Jiradet; Baudrimont, Antoine; Machacek, Thomas; Woglar, Alexander; Csaszar, Edina; Pasierbek, Pawel; Ammerer, Gustav; Gruenbaum, Yosef; Jantsch, Verena (2009). Meiotic chromosome homology search involves modifications of the nuclear envelope protein Matefin/SUN-1. CELL;139 :920-933. PMID: 19913286
Doctoral Program 'Chromosome Dynamics'
The Group Jantsch participates in in the special Doctoral Program 'Chromosome Dynamics' reviewed and funded by the Austrian Research Fund FWF.