A single-cell resolution map of dynamic mRNA regulatory programs during the maternal-to-zygotic transition of zebrafish embryos

The expression of every gene during development is tightly regulated by the interplay of mRNA transcription and degradation. By changing one or more of these rates, cells produce complex expression patterns that help in establishing distinct cell identities. While the role of mRNA transcription in these events is well established, accumulating evidence also highlight the role of mRNA degradation in shaping developmental gene expression patterns. This is particularly important during the maternal-to-zygotic transition, as embryos undergo a massive degradation of maternal mRNAs and produce new zygotic transcripts to replace them. But distinguishing the unique contributions of mRNA transcription and degradation to gene regulation remains a challenge. Therefore, the role of mRNA degradation in these events is still not fully understood. We combine single-cell transcriptomics with RNA metabolic labeling and nucleotide conversion, to systematically monitor the interplay between maternal and zygotic transcripts during zebrafish maternal-to-zygotic transition at cellular resolution. We show that most cell-type restricted expression arises by transcription of zygotic genes, but distinguish a unique role for degradation in restricting the maternal expression of specific genes to primordial germ cells. We further establish the sequence-based rules for this unique phenomenon. Finally, we quantify degradation rates of maternal mRNAs and accumulation rates of zygotic mRNAs, and find differences between genes and cell-lineages. These associate a fast replacement kinetics with a cell-type or time restricted zygotic expression. Our approach provides valuable resource to investigate the maternal and zygotic transcriptomes, and to highlight post-transcriptional events that control gene regulation during early embryogenesis.