Special Seminar : Towards reconstituting human somitogenesis & congenital diseases of the spine in vitro
Event details
| Date | 02.11.2022 |
| Hour | 14:00 › 15:00 |
| Speaker |
Cantas Alev M.D., Ph.D. Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan |
| Location | |
| Category | Conferences - Seminars |
| Event Language | English |
Special Seminar hosted by Can Aztekin - Elisir Scholar
Any PIs or postdocs / students who would be interested in participating in a one-to-one meeting with Prof. Alev, please contact Can Aztekin to arrange
Cantas Alev M.D., Ph.D.
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
Abstract:
"Somitogenesis, a core developmental event during which the metameric body plan of vertebrates is laid out, has been extensively studied using model organisms such as mouse, chick or zebrafish, but remains largely elusive and poorly understood when it comes to human and other primates. Using in vitro-derived presomitic mesoderm (PSM), we previously succeeded to quantify oscillatory activity of the segmentation clock, a molecular oscillator believed to control somite formation. Interestingly, these in vitro models of the segmentation clock did not show any sign of segmentation or somitogenesis despite the presence of oscillatory activity of clock genes such as HES7. Extending on these earlier findings we then asked whether we could recapitulate not only the clock but also the actual process of segmentation and epithelial somite formation in vitro. Utilizing again pluripotent stem cells as starting material we established a 3D in vitro model of human somitogenesis, which exhibited periodic formation of properly patterned epithelial somites in synchrony with the segmentation clock. Our selforganizing “axioloids” shared further morphological and molecular features of the human embryo and emerging vertebrate embryonic axis including presence of opposing morphogen gradients. We also demonstrated a critical role of Retinoic Acid (RA) signalling in the stabilisation of segments, suggesting synergy of RA and ECM in the formation and epithelialisation of somites. Lastly, we applied our bottom-up model system to study the pathogenesis of human congenital diseases of the spine, using patient-like iPSC cells with mutations in HES7 and MESP2, which revealed disease-associated phenotypes including loss of epithelial somite formation and abnormal rostrocaudal patterning. These results suggest that axioloids represent a promising novel platform to study axial development and disease in humans".
Any PIs or postdocs / students who would be interested in participating in a one-to-one meeting with Prof. Alev, please contact Can Aztekin to arrange
Cantas Alev M.D., Ph.D.
Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Kyoto, Japan
Abstract:
"Somitogenesis, a core developmental event during which the metameric body plan of vertebrates is laid out, has been extensively studied using model organisms such as mouse, chick or zebrafish, but remains largely elusive and poorly understood when it comes to human and other primates. Using in vitro-derived presomitic mesoderm (PSM), we previously succeeded to quantify oscillatory activity of the segmentation clock, a molecular oscillator believed to control somite formation. Interestingly, these in vitro models of the segmentation clock did not show any sign of segmentation or somitogenesis despite the presence of oscillatory activity of clock genes such as HES7. Extending on these earlier findings we then asked whether we could recapitulate not only the clock but also the actual process of segmentation and epithelial somite formation in vitro. Utilizing again pluripotent stem cells as starting material we established a 3D in vitro model of human somitogenesis, which exhibited periodic formation of properly patterned epithelial somites in synchrony with the segmentation clock. Our selforganizing “axioloids” shared further morphological and molecular features of the human embryo and emerging vertebrate embryonic axis including presence of opposing morphogen gradients. We also demonstrated a critical role of Retinoic Acid (RA) signalling in the stabilisation of segments, suggesting synergy of RA and ECM in the formation and epithelialisation of somites. Lastly, we applied our bottom-up model system to study the pathogenesis of human congenital diseases of the spine, using patient-like iPSC cells with mutations in HES7 and MESP2, which revealed disease-associated phenotypes including loss of epithelial somite formation and abnormal rostrocaudal patterning. These results suggest that axioloids represent a promising novel platform to study axial development and disease in humans".
Practical information
- Informed public
- Free
Organizer
- Can Aztekin, PhD, Group Leader - ELISIR Scholar - Branco Weiss Fellow
Contact
- Marie-France Radigois, Administrative Assistant