Spindle Brain Organoid · Understanding cellular mechanisms of human brain development using cerebral organoids
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-09-01 → 2019-08-31
- EU contribution
- €166,157
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Understanding cellular mechanisms of human brain development using cerebral organoids
The human brain is the centre of human cognitive abilities. It is made of billions of neurons that are produced during fetal development. Human brain development differs substantially from rodents and the underlying mechanisms of its development and neurodevelopmental disorders are poorly understood. Human brain organoids are novel 3D stem cells-derived human models developed that recapitulate human-specific features of brain development with great accuracy. These emerging systems offer the opportunity to perform functional studies of human brain development and investigate mechanisms underlying human brain disorders with unprecedented accuracy. The goals of the project was to establish assays for a better experimental manipulation in brain organoid models and to gain insights into the mechanisms that control human brain development and that, when defective, lead to a smaller brain, a condition called microcephaly.
Data: CORDIS, © European Union
Project objective
The development of the human brain is a key and fascinating question in neurobiology. Studies in model organisms have provided enormous insight into basic mechanisms of neurogenesis, which relies on the balance between proliferation and differentiation of neural stem cells. Although human neurogenesis follows the same principles, human specific processes that lead to human brain expansion are largely unclear. In vitro models that recapitulate human brain development are invaluable tools to provide insight into human specific processes and brain expansion. In this application, I propose to use human cerebral organoids, a novel in vitro model system of human brain development, to investigate human specific mechanisms of brain development.Studies in primates suggest that the orientation of the mitotic spindle in neural stem cell divisions may be a key factor driving the expansion of the human brain. In order to gain insight into the role of spindle orientation in human brain development, I will use cerebral organoids to investigate how changes in spindle orientation affect proliferation of human neural stem cells and their differentiation into neural fates. To induce changes in spindle orientation in cerebral organoids, I will inactivate known regulators of spindle orientation. For this, I will establish an inducible loss-of-function system in human embryonic stem cells to inactivate such regulators in a controlled manner during the development of cerebral organoids. By using live-imaging techniques in such organoids, I will analyse how changes in spindle orientation affect the outcome of neural stem cell divisions. Then, by using immunohistochemical analysis, I will examine how changes in spindle orientation influence neuronal layering and cortical architecture. Overall, I expect to gain insight into the role of spindle orientation in human brain development and into the mechanisms underlying human brain expansion.
Original text from CORDIS.
Participants
- INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH · WienCoordinatorAustria
Links
Data: CORDIS, © European Union