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Embryonic development, wound healing and regeneration pose an interesting problem for biophysicists, since the complex cell rearrangements and tissue dynamics they invlove have to be robust against environmental changes, suggesting that generic physical mechanisms play an important role for these processes.

From a physics perspective, biological tissues are active complex fluids. They are active, because the tissue constituents, the cells, continuously consume energy by ATP hydrolysis, which allows them to divide, move within the cell association and interact with their neighboring cells. They are complex fluids, because they behave as elastic solids on short time scales and as viscous fluids on long time scales.

In order to understand the complexity of tissue structure and dynamics, the problem has to be addressed on multiple length scales: From the underlying molecular machinery to the physical properties of the cytoskeleton and the cell membrane that determine the structure and migratory behavior of individual cells, to the mechanisms of the adhesion machinery that governs cell-cell-interaction in the tissue, up to the physical properties of multicellular aggregates and whole tissues.

We combine tools from physics, material science, genetics and molecular biology to gain a better understanding of the the forces driving cell movement and tissue formation during embryogenesis in zebrafish and planarians (flatworms), as well as during wound healing and regeneration in planarians.

Planarians are members of the phylum Platyhelminthes, the flatworms. They have served as a model system to study development and regeneration for more than 200 years. Planarian regeneration relies on the presence of adult stem cells, called neoblasts. Planarians consist of approximately 30% neoblasts, and according to the "father of the fruit fly", T.H. Morgan a piece 279th the size of the original worm is able to regenerate a fully developed new specimen.

piwi1

piwi1 insitu shows distribution of neoblasts

Research on planarians has traditionally focused on surgical and pharmacological manipulations. Only recently, molecular methods such as in situ hybridizations, immunocytology, and RNAi have been successfully applied. By complementing the molecular methods with biophysics approaches, we hope to gain a deeper insight into the basic mechanisms accounting for regeneration and stem-cell regulation.

Little is known about planarian embryogenesis. The most detailed descriptions are more than 100 years old drawings. At the beginning of development, planarian embryos are ectolecithal, i.e. yolk cells reside outside the embryo. Then, they form a temporary pharynx and gut, which allows them to internalize the yolk cells. These structures are not part of the hatchling; they disappear again at later stages when the final body structures are forming. We are aiming to develop imaging and labeling tools that allow us to gain a deeper insight into the principles of planarian embryonic development.

We are interested in the forces that cause cell and tissue movements during early zebrafish gastrulation. Gastrulation is the central process through which blastoderm cells rearrange to form the three primary germ layers: ectoderm, mesoderm, and endoderm. In zebrafish, gastrulation starts at around 50% epiboly, a point at which the blastoderm has spread and covered half of the large yolk cell,
and with the internalization of hypoblast cells near the blastoderm margin at the dorsal side of the gastrula. Progressive single cell ingression and convergence movements, causing cell compaction at the dorsal blastoderm margin, lead to the formation of the embryonic organizer (shield), the analog of the amphibian Spemann organizer. Once internalized, mesendoderm progenitors migrate as a cohesive group of cells away from the blastoderm margin and towards the animal pole of the gastrula. We are studying the forces that are in play during these cell and tissue movements by rheological measurements of cell and tissue properties in vitro as well as extensive in vivo imaging and cell tracking.

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