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 medical and health sciencesclinical medicineobstetricsfetal medicinemedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineembryologymedical and health scienceshealth sciencesinfectious diseasesDNA virusesmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH Net EU contribution € 166 156,80 Address DR BOHRGASSE 3 1030 Wien Austria See on map Region Ostösterreich Wien Wien Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 166 156,80