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Understanding cellular mechanisms of human brain development using cerebral organoids

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.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2015

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Coordinator

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 166 156,80
Address
DR BOHRGASSE 3
1030 WIEN
Austria

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Region
Ostösterreich Wien Wien
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 166 156,80
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