Roles of the pluripotency associated Tex19.1 gene in mouse embryonic and germline development

Abstract

Chromosome segregation errors that occur in the developing germline generate aneuploidies which are among the leading causes of embryonic lethality, spontaneous abortions and chromosomal disorders, such as Down’s syndrome.

Compared to other species, human oocytes appear to be particularly prone to suffer chromosome missegregation and the risk of aneuploid pregnancies in humans increases drastically with maternal age. Despite its particular importance for human health, relatively little is known about the basis for the high incidence of aneuploidies in human oocytes and the maternal-age effect. The identification and analysis of molecular pathways that promote genetic and chromosomal stability is important for our understanding of mechanisms that lead to aneuploidy and how it can be prevented.

Here, I examine the role of the pluripotency associated Tex19.1 gene, in preventing aneuploidy during mouse female germ cell development. I demonstrate that Tex19.1-/- females are subfertile when mated with wild type males due to defects in chromosome segregation during meiosis. In contrast to Tex19.1-/- male gem cells, synaptonemal complex formation appears to be completed normally in Tex19.1-/- females but high levels of aneuploidy are evident during the second meiotic stages of oogenesis. The Tex19.1-/- females transmit these aneuploidies to their offspring likely resulting in the observed embryonic death and subfertility.

In addition to its role in the female germline, I investigated the function of Tex19.1 during embryonic development. I found that Tex19.1-/- knockout mice are born at a sub- Mendelian frequency and this reduction is exacerbated in diapaused embryos, suggesting that Tex19.1 plays a role during a stage where a pluripotent state is maintained for a prolonged period of time. Furthermore, I identified high levels of aneuploidy accumulating in pluripotent stem cells in the absence of Tex19.1.