Objetivo 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. Ámbito científico 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 Programa(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 Tema(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Convocatoria de propuestas H2020-MSCA-IF-2015 Consulte otros proyectos de esta convocatoria Régimen de financiación MSCA-IF-EF-ST - Standard EF Coordinador INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH Aportación neta de la UEn € 166 156,80 Dirección DR BOHRGASSE 3 1030 Wien Austria Ver en el mapa Región Ostösterreich Wien Wien Tipo de actividad Private for-profit entities (excluding Higher or Secondary Education Establishments) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Participación en los programas de I+D de la UE Opens in new window Red de colaboración de HORIZON Opens in new window Coste total € 166 156,80