Vergleichende Analyse der Regenerationsfähigkeiten verschiedener Planarienarten.
Entwicklungsbiologie
Zusammenfassung der Projektergebnisse
Planarians are a group of flatworms that are capable of fascinating feats of regeneration. Even when cut into tiny tissue pieces, some species manage to regenerate each piece back into a complete and perfectly proportioned animal. However, other planarian species can only regenerate pieces cut from specific body regions or are completely regeneration incompetent. As a taxonomic group, planarians, therefore, promise a unique opportunity to study how regeneration works at the level of genes and molecules, the specific alterations in these mechanisms that cause regeneration defects, and also the evolutionary processes that ultimately shape the regenerative abilities of a species in interplay with the environment. The specific objective of this research project was to carry out genome comparisons between a non-regenerating planarian species and two closely related regeneration-competent species. Specifically, the project aimed to generate i) high-quality genome assemblies of the three species, ii) RNAseq time courses documenting which genes are expressed when during successful versus abortive regeneration, and finally, iii) ATACseq time courses as a method to reveal the regulatory control sequences in the genomes and to potentially explain speciesspecific differences in gene expression dynamics and regeneration. Two unexpected discoveries required a change of plans early on. First, we found that the three species were largely refractory to RNAi, the so far only technique in planarians to experimentally modulate gene function and thus to test the results of sequencing experiments. Second, we discovered that the genomes of the three species simply cannot be pieced together with the current sequencing technologies. The originally intended comparative analysis of regenerative abilities was therefore not feasible and we decided to utilize the funds for a more general analysis of the gene regulatory basis of planarian regeneration and regeneration defects. Altogether, we achieved the following: 1) End-to-end genome assembly and gene annotations of the model species Schmidtea mediterranea, and similar high-quality genome assemblies of four other planarian species and strains. 2) Transcriptome sequencing of planarian species that we brought into the lab and gene expression time series in response to wounding in several species. 3) Annotation of the gene regulatory regions that drive gene expression in four species. These efforts have so far contributed to a manuscript on the evolution of planarian regeneration that shows that regenerative abilities can change rapidly in evolution, always seem to involve changes in the activity of a particular signaling pathway (Wnt signaling), and may relate to additional roles of this pathway in sexual reproduction. This provides first insights into both how and why planarian regeneration defects might arise in nature, which is an intriguing question in the face of "survival of the fittest”. In addition, our efforts resulted in a complete end-to-end assembly of the genome sequence of 5 planarian strains and species, which represent very important resources for all scientists trying to understand planarian regeneration. PlanMine, our planarian web resource, already hosts some of the data.
