Projektbeschreibung
Neue Studie will die Mechanismen der Musterbildung von Gewebe ans Licht bringen
Das EU-finanzierte Projekt ACE-OF-SPACE will eine jahrhundertealte Frage der Entwicklungsbiologie beantworten: Wie funktioniert die Musterbildung von Gewebe in Zeit und Raum und wie differenzieren sich identische Zellen, um den Bauplan des ausgewachsenen Individuums zu bilden? Diese Musterbildungsvorgänge werden von einer Reihe von Signalmolekülen koordiniert. Noch ist jedoch unklar, wie genau diese Signale übermittelt werden und wie Zellen miteinander interagieren, um diese Informationen zu deuten. Außerdem hat es sich als schwierig erwiesen, direkt zu visualisieren, wie Signalmoleküle die Musterbildung von Embryos umsetzen, und die Mindestanforderungen der autonomen Musterbildung zu ermitteln. Das Projekt wird an Embryonen von Zebrafischen, embryonalen Stammzellen von Mäusen und Bakterienkolonien arbeiten. Die Ergebnisse werden spannende Erkenntnisse über die Kommunikation zwischen Zellen sowie über die Gewebezüchtung liefern.
Ziel
A central problem in developmental biology is to understand how tissues are patterned in time and space - how do identical cells differentiate to form the adult body plan? Patterns often arise from prior asymmetries in developing embryos, but there is also increasing evidence for self-organizing mechanisms that can break the symmetry of an initially homogeneous cell population. These patterning processes are mediated by a small number of signaling molecules, including the TGF-β superfamily members BMP and Nodal. While we have begun to analyze how biophysical properties such as signal diffusion and stability contribute to axis formation and tissue allocation during vertebrate embryogenesis, three key questions remain. First, how does signaling cross-talk control robust patterning in developing tissues? Opposing sources of Nodal and BMP are sufficient to produce secondary zebrafish axes, but it is unclear how the signals interact to orchestrate this mysterious process. Second, how do signaling systems self-organize to pattern tissues in the absence of prior asymmetries? Recent evidence indicates that axis formation in mammalian embryos is independent of maternal and extra-embryonic tissues, but the mechanism underlying this self-organized patterning is unknown. Third, what are the minimal requirements to engineer synthetic self-organizing systems? Our theoretical analyses suggest that self-organizing reaction-diffusion systems are more common and robust than previously thought, but this has so far not been experimentally demonstrated. We will address these questions in zebrafish embryos, mouse embryonic stem cells, and bacterial colonies using a combination of quantitative imaging, optogenetics, mathematical modeling, and synthetic biology. In addition to providing insights into signaling and development, this high-risk/high-gain approach opens exciting new strategies for tissue engineering by providing asymmetric or temporally regulated signaling in organ precursors.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencessynthetic biology
- natural sciencesbiological sciencesdevelopmental biology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineembryology
- natural sciencesmathematicsapplied mathematicsmathematical model
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
78464 Konstanz
Deutschland