Zygotic Cell Fate and Parent-Biased Gene Expression in Fission Yeast

ongoing

As two gametes fuse, the newly formed zygote immediately represses mating, to prevent polyploid formation, and triggers the developmental program that gives rise to a new individual. My work showed that zygotes of fission yeast and higher eukaryotes bare striking similarities, and here I propose to use this powerful model system to explore the basic mechanisms of gamete-to-zygote transition. Working in fission yeast, where gametes and zygotes are well-defined and accessible to outstanding plethora of experimental approaches, will show how different regulatory mechanisms synergize to execute this key cell fate switch. Our first aim explores zygotic regulation of gene expression and mating blocks. First, to show how zygote-specific signaling propagates, we will identify its targets using biochemical screens. Second, we will analyse how zygotes alter gene expression. High-throughput sequencing will show transcriptional dynamics and genetics approaches will test its regulation and relevance. Third, we will combine microscopy and genetics to reveal the workings of fungal re-fertilization blocks. Our second aim explores roles and regulation of the parent-biased allele expression in fungal zygotes that I recently discovered. While biochemical and sequencing-based screens will identify genes asymmetrically expressed from parental genomes, genetics strategies will test their roles. A structural biology workpackage will show how a simple homeodomain transcription factor drives the bias between parental genomes. Similarities between zygotes of fission yeast and higher eukaryotes hint to the relevance of our work for other developmental systems. By understanding fungal blocks to re-fertilization, which have been previously completely overlooked, we may identify their conserved principles, as increasingly evident for other sexual processes. Finally, exploring the bias in expression of parental alleles in yeast may help explain its recurrence in distant plant and animal lineages.