Characterising the role of TEX12 in centrosome and cilia development

Cell division is a fundamental process critical for the growth, development, and reproduction of living organisms. In mammals, there are two distinct types of cell division, mitosis and meiosis. Mitosis allows us to regenerate somatic cells by generating two daughter cells identical to the mother cell. In contrast, meiosis is essential for sexual reproduction and is characterised by the reduction of chromosome number resulting in four genetically diverse haploid daughter cells. To achieve this meiotic cell division involves a series of synchronised chromosome movements culminating in genetic recombination which ensures the diversity of the species. The intricate nature of meiosis is delivered by a specialised synaptonemal complex structure generally assumed to have no biological function other than facilitating genomic rearrangements in meiosis. Consequently, synaptonemal complex proteins are believed to be silenced in healthy somatic cells to prevent genomic instability during mitosis.
However, when investigating the effects of losing a synaptonemal complex gene called TEX12 we unexpectedly observed abnormal brain development and obesity. These phenotypes can be associated with a set of disorders called ciliopathies characterised by defects in the structure and function of cilia. Cilia are small hair-like structures found on the surface of some cells where they play a key role in cellular processes such as sensing and passing on signals. This project will employ live cell imaging and gene editing to determine the role TEX12 plays in cilia formation. Furthermore, we will identify regulators of TEX12 expression to understand when it is normally produced outside of meiosis. This cross-disciplinary approach will allow us to characterise if TEX12 is one of the causes of ciliopathy in patients.