| Project Detail |
The development of a multicellular organism requires the precise control of gene expression in space and time so that cells adopt their correct identity. However, genetic mutations can alter this complex process. Recently, transcriptional adaptation (TA) has been uncovered as one of the mechanisms underlying genetic compensation in zebrafish, mouse cells in culture, and Caenorhabditis elegans. TA refers to the phenomenon by which mutated genes (often with mRNA-destabilizing mutations) trigger the transcriptional modulation of related genes, called adapting genes. However, little is known about the spatial and temporal characteristics of adapting gene regulation and particularly during the zygotic genome activation. This project aims to decipher when and where TA occurs during early zebrafish development. Using genome engineering followed by live imaging, high-resolution microscopy and quantitative analysis, I will test the hypothesis that TA is regulated in a temporal manner during zygotic genome activation and that there is a specific mode of transcription during the modulation of the adapting genes (i.e. linear/discontinuous). Furthermore, I will investigate the subcellular localization of mutant mRNA degradation as well as the heterogeneity of the TA response between embryonic cells. Finally, I will implement the live imaging of translation in zebrafish embryo to decipher whether the dynamics of translation is involved during the TA/genetic compensation process.
Until now, TA has been mostly investigated on pooled populations of cells. Therefore, we lack the understanding of this phenomenon at the single cell level. This project aims to fill this gap and obtain a better understanding of the spatio-temporal characteristics of genetic compensation which aid in the robustness of vertebrate development. |
