Meiosis is a specialized reductional cell division by which sexual organisms produce gametes that can join to give rise to euploid offspring. The mechanisms that enable the accurate segregation of homologous chromosomes in the first meiotic division have been studied in many organisms. Yet, a detailed molecular characterization of meiosis has not been carried out in any member of the lophotrochozoa, a large and diverse animal clade that includes molluscs, rotifers, annelid worms, and flatworms.
I have conducted an initial characterization of homolog pairing and recombination initiation in a novel model lophotrochozan, the freshwater planarian Schmidtea mediterranea. Like many species, these organisms form a telomere bouquet in early meiotic prophase. This bouquet normally persists throughout pachytene, and disruption of the telomere bouquet via depletion of the nuclear envelope protein Smed-SUN1 both disrupts homolog pairing and results in non-homologous synapsis.
This work has also revealed a telomere-proximal enrichment of double strand DNA breaks (DSBs), represented by Smed-RAD51 foci, and shown that DSB formation is dependent on the axial element protein Smed-HOP1. Depletion of HOP1 also disrupts progression through meiosis, and nuclei arrest in the bouquet stage without obvious homolog pairing or synaptonemal complex polymerization. Preliminary characterization of Smed-SMC3 suggests that partial loss of sister chromatid cohesion also disrupts homolog pairing, synapsis, and progression through meiosis.
This work introduces a number of novel tools and protocols for use in S. mediterranea, demonstrates that planarian spermatogenesis is a tractable model for the study of meiosis, and also suggests the existence of intriguing mechanisms that control homolog pairing, recombination and synapsis in this animal.
|Advisor:||Dernburg, Abby F.|
|Commitee:||Cande, W. Zacheus, Glass, Louise, Weisblat, David|
|School:||University of California, Berkeley|
|Department:||Molecular and Cell Biology|
|School Location:||United States -- California|
|Source:||DAI-B 75/01(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Cellular biology|
|Keywords:||Horma, Meiosis, Planarian, Schmidtea, Spermatogenesis, Sun|
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