Descripción del proyecto
Un nuevo estudio busca desvelar los mecanismos de la formación de patrones tisulares
El proyecto financiado con fondos europeos ACE-OF-SPACE abordará una pregunta centenaria en el campo de la biología del desarrollo. ¿Cómo se determina la formación de patrones tisulares en el tiempo y el espacio, y cómo se diferencian células idénticas para formar el plano corporal adulto? Dichos procesos de formación de patrones están coordinados por una serie de moléculas de señalización. Sin embargo, todavía no está claro cómo se transmiten exactamente estas señales y cómo interactúan las células entre sí para interpretar esta información. Además, ha sido complicado visualizar directamente cómo las moléculas señalizadoras determinan la formación de patrones en embriones y definir los requisitos mínimos para la formación de patrones autoorganizados. El proyecto trabajará con embriones de pez cebra, células madre embrionarias de ratón y colonias bacterianas. Los resultados proporcionarán información interesante sobre la comunicación entre células y la ingeniería tisular.
Objetivo
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.
Ámbito científico
- natural sciencesbiological sciencessynthetic biology
- natural sciencesbiological sciencesdevelopmental biology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineembryology
- natural sciencesmathematicsapplied mathematicsmathematical model
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
78464 Konstanz
Alemania