Project description:miRNAs play essential roles in the mechanics of gene regulation, however, on an organismal-scale, the processes in they are deployed are not well understood. Here, we adopt an evolutionary developmental approach to study miRNA function by examining their expression throughout embryogenesis in both C. elegans and D. melanogaster. We find that, in both species, the miRNA complement of the transcriptome shifts in a punctuated fashion during the previously identified mid-developmental transition specifying two dominant modes of miRNA expression: an early and a late profile. Strikingly, we find that phylogenetically conserved miRNAs are expressed late, while early expressed miRNAs are inversely expressed with their targets suggesting strong target-inhibition. Our work exposes two distinct strategies of miRNA function comprising late-expressed physiological roles and early expressed repressive roles. In summary, the expression of miRNAs throughout embryogenesis in two species implicates their role in the canalization of cell-types during late phases of embryogenesis and repressing targets to lock-down misexpression.
Project description:miRNAs play essential roles in the mechanics of gene regulation, however, on an organismal-scale, the processes in they are deployed are not well understood. Here, we adopt an evolutionary developmental approach to study miRNA function by examining their expression throughout embryogenesis in both C. elegans and D. melanogaster. We find that, in both species, the miRNA complement of the transcriptome shifts in a punctuated fashion during the previously identified mid-developmental transition specifying two dominant modes of miRNA expression: an early and a late profile. Strikingly, we find that phylogenetically conserved miRNAs are expressed late, while early expressed miRNAs are inversely expressed with their targets suggesting strong target-inhibition. Our work exposes two distinct strategies of miRNA function comprising late-expressed physiological roles and early expressed repressive roles. In summary, the expression of miRNAs throughout embryogenesis in two species implicates their role in the canalization of cell-types during late phases of embryogenesis and repressing targets to lock-down misexpression.
Project description:miRNAs play essential roles in the mechanics of gene regulation, however, on an organismal-scale, the processes in they are deployed are not well understood. Here, we adopt an evolutionary developmental approach to study miRNA function by examining their expression throughout embryogenesis in both C. elegans and D. melanogaster. We find that, in both species, the miRNA complement of the transcriptome shifts in a punctuated fashion during the previously identified mid-developmental transition specifying two dominant modes of miRNA expression: an early and a late profile. Strikingly, we find that phylogenetically conserved miRNAs are expressed late, while early expressed miRNAs are inversely expressed with their targets suggesting strong target-inhibition. Our work exposes two distinct strategies of miRNA function comprising late-expressed physiological roles and early expressed repressive roles. In summary, the expression of miRNAs throughout embryogenesis in two species implicates their role in the canalization of cell-types during late phases of embryogenesis and repressing targets to lock-down misexpression.
Project description:Transcriptomic studies typically examine expression at the gene level, although it has been long recognized that the same genetic locus may produce isoforms distinct in their splicing and site of polyadenylation. Here we examine alternatively polyadenylated (APA) transcripts throughout embryogenesis and discover distinct strategies for gene regulation. We introduce APA-Seq, an RNA-Seq method to study APA at a global level, and apply it to study individual C. elegans embryos throughout early development. Surprisingly, we find that genes, whose overall expression is constitutive throughout development, generally show highly dynamic expression for individual isoforms. Such genes tend to participate in cellular as opposed to developmental processes, and this trend was also evident in the closely related C. japonica nematode, providing evidence that the manner by which cellular processes are regulated during embryogenesis is evolutionarily conserved. Finally, we report that genes with dynamic isoform usage have significantly more miRNA binding sites relative to constitutively-expressed isoforms, suggesting strong miRNA regulation in the control of isoform expression. Our findings support a model distinguishing two modes of gene regulatory underlying embryonic development each with unique functions and mechanisms.
Project description:Classical embryological studies revealed that during mid-embryogenesis vertebrates show similar morphologies. This “phylotypic stage” has recently received support from transcriptome analyses, which have also detected similar stages in nematodes and arthropods. A conserved stage in these three phyla has led us to ask if all animals pass through a universal definitive stage as a consequence of ancestral constraints on animal development. Previous work has suggested that HOX genes may comprise such a ‘zootypic’ stage, however this hypothetical stage has hitherto resisted systematic analysis. We have examined the embryonic development of ten different animals each of a fundamentally different phylum, including a segmented worm, a flatworm, a roundworm, a water bear, a fruitfly, a sea urchin, a zebrafish, a sea anemone, a sponge, and a comb jelly. For each species, we collected the embryonic transcriptomes at ~100 different developmental stages and analyzed their gene expression profiles. We found dynamic gene expression across all of the species that is structured in a stage like manner. Strikingly, we found that animal embryology contains two dominant modules of zygotic expression in terms of their protein domain composition: one involving proliferation, and a second involving differentiation. The switch between these two modules involves induction of the zootype; which in addition to homeobox containing genes, also involves Wnt and Notch signaling as well as forkhead domain transcription factors. Our results provide a systematic characterization of animal universality and identify the points of embryological constraints and flexibility.
Project description:Classical embryological studies revealed that during mid-embryogenesis vertebrates show similar morphologies. This âphylotypic stageâ has recently received support from transcriptome analyses, which have also detected similar stages in nematodes and arthropods. A conserved stage in these three phyla has led us to ask if all animals pass through a universal definitive stage as a consequence of ancestral constraints on animal development. Previous work has suggested that HOX genes may comprise such a âzootypicâ stage, however this hypothetical stage has hitherto resisted systematic analysis. We have examined the embryonic development of ten different animals each of a fundamentally different phylum, including a segmented worm, a flatworm, a roundworm, a water bear, a fruitfly, a sea urchin, a zebrafish, a sea anemone, a sponge, and a comb jelly. For each species, we collected the embryonic transcriptomes at ~100 different developmental stages and analyzed their gene expression profiles. We found dynamic gene expression across all of the species that is structured in a stage like manner. Strikingly, we found that animal embryology contains two dominant modules of zygotic expression in terms of their protein domain composition: one involving proliferation, and a second involving differentiation. The switch between these two modules involves induction of the zootype; which in addition to homeobox containing genes, also involves Wnt and Notch signaling as well as forkhead domain transcription factors. Our results provide a systematic characterization of animal universality and identify the points of embryological constraints and flexibility. 139 single embryo samples.