Shape and proportion regulation during regeneration
Previous and Current Research
Our lab studies the astonishing regenerative abilities of planarian flatworms. Despite their complex internal anatomy, these animals can regenerate their entire being from tiny tissue fragments. Such transformation of a random tissue piece back into a complete and healthy animal raises a number of fascinating questions. For example, how can the remaining tissue “know” what’s missing? Why is it that in a world shaped by survival of the fittest, only a minority of animals are able to regenerate? What encodes the shape of the planarian body plan and how can tissues in general measure and maintain proportions?
Taking full advantage of the interdisciplinary research environment in Dresden, we bring cell biology, genomics and physics to bear on making progress in these questions. One focus is the identification of the signaling pathways that shape the planarian body plan. We use RNAi screening and deep sequencing to identify components and understand their interactions. We raise antibodies and develop staining protocols to visualize their activity in tissues. So far, this approach has highlighted the crucial importance of the Wnt/bCatenin signaling pathway in specifying head/tail identity: b-Catenin-RNAi induces double-headed animals, but excessive activity causes double-tails. Translating the activity of patterning pathways into the anatomical manifestations of a body plan necessitates cross-talk between patterning signals and differentiating cells. The only source of new cells in planarians are highly abundant pluripotent adult stem cells. Their continuous divisions, precisely matched by the death of old cells, drives the steadys self-renewal of the entire animal. Feeding shifts the steady state towards addition of new cells by causing a brief burst of increased stem cell divisions. Starvation shifts the balance towards a net loss of cells, thus literally shrinking the animals (“de-growth”). In collaboration with the Juelicher group at the MPI-PKS and the Brusch group at the TUD, we are trying to understand the mechanistic basis of the dynamic steady state in close interplay between experiment and theory. Lastly, we have recently started to populate the lab with exotic species of planarians. Hundreds of species are known to exist with many remaining to be discovered and fascinatingly, not all planarians regenerate very well. For this reason, we have initiated a worldwide collection effort and now keep more than 50 species at the MPI-CBG. As a proof-of-principle for working with non-model planarians, we demonstrated that the posterior head regeneration defect in the species D. lacteum is due to miss-regulation of Wnt-signaling and that alterations of pathway activity can rescue head regeneration. In collaboration with the groups of Michael Hiller and Gene Myers, we are now systematically exploring the mechanisms underlying the evolutionary gain and loss of regenerative abilities, as well as the tremendous biodiversity of shapes, tissue turn-over rates or life spans that is apparent in the planarian species collection.
Future Projects and Goals
- The molecular coordinate system of the planarian body plan: Visualizing, quantifying and modeling the dynamic network of patterning cues during regeneration and growth/de-growth.
- Interplay between patterning signals and the pluripotent stem cell system: How are patterning signals “translated” into the anatomical distribution of cell types, tissues and organs and how is stability maintained in face of constant turn-over?
- Planarian Evo-devo: Obtaining molecular insights into evolutionary variation of regenerative abilities, pattern formation, body shape or life spans by mining the tremendous biodiversity present in our planarian species collection.
Methodological and Technical Expertise
- Planarian regeneration
- Antibody production and staining of whole mounts and tissue sections.
- Quantitative Western Blotting
- In situ hybridization of whole mounts and tissue sections
- Next generation Sequencing and NGS data analysis
- Genome sequencing, assembly and annotation.
S.-Y. Liu, C. Selck, B. Friedrich, R. Lutz, M. Vila-Farré, A. Dahl, H. Brandl, N. Lakshmanaperumal, I. Henry & J. C. Rink
Reactivating head regrowth in a regeneration-deficient planarian species.
Nature, in press
Stem cell systems and regeneration in planaria.
Dev. Genes Evol., 223, no. 1-2, pp. 67–84, (2013)
Rink, Jochen; Vu, Hanh Thi-Kim; Alvarado, Alejandro Sánchez
The maintenance and regeneration of the planarian excretory system are regulated by EGFR signaling.
Development, 138, no. 17, pp. 3769–3780, (2011)
Rink, Jochen; Gurley, Kyle A; Elliott, Sarah A; Alvarado, Alejandro Sánchez
Planarian Hh signaling regulates regeneration polarity and links Hh pathway evolution to cilia.
Science, 326, no. 5958, pp. 1406–1410, (2009)
Gurley, Kyle A; Rink, Jochen; Alvarado, Alejandro Sánchez
Beta-catenin defines head versus tail identity during planarian regeneration and homeostasis.
Science, 319, no. 5861, pp. 323-327, (2008)