Rosette NSC Screen · Mechanisms of Neurogenesis from Drosophila to Human
FP7 — People (Marie Curie Actions)
- Duration
- 2013-03-01 → 2015-06-30
- EU contribution
- €187,888
- Participants
- 1
- Scheme
- MC-IIF
Lines connect the coordinator with its partners.
Results in brief
Mechanisms of Neurogenesis from Drosophila to Human
The goals of this project were to establish an in vitro method to examine mechanisms of human brain development in vivo. This project has been extremely successful in that it has lead to the establishment of an entirely novel 3D method for generation of human brain tissue. Madeline has successfully established human stem cell work in the lab, and has used pluripotent stem cells to differentiate so-called cerebral organoids. The organoids have been successfully used to examine mechanisms of human neural stem cell division and differentiation as set out in the initial aims of the project. The project did not lead to a screen for novel candidate genes, as initially planned, since the new 3D method does not lend itself to high throughput screening. However, it is instead highly useful for examining complex mechanisms of brain development in a hypothesis driven manner. These organoids will continue to be used in the lab and the method is currently being established and successfully implemented in many external laboratories through collaborations and independent research projects.
Data: CORDIS, © European Union
Project objective
Neurogenesis in the mammalian neocortex depends upon asymmetric cell divisions to maintain a balance between self-renewal and neuronal differentiation. This process is likely a key element governing the expansion of the human cerebral cortex, and its disruption can lead to severe developmental disorders such as microcephaly and lissencephaly. However, mechanisms of asymmetric cell division in mammalian brain development are largely unclear, and its potential role in human cortical development has not been examined. Substantial headway has been made in understanding mechanisms of asymmetric cell division in the Drosophila central nervous system. Our lab has recently published a genome-wide RNAi screen, which has identified several novel regulators of asymmetric cell division in Drosophila. To test whether these newly identified factors have conserved roles in mammals, I will use mouse neural rosettes to screen and perform functional assessments of the promising candidates. I will then perform functional studies of human neural rosettes to test our candidates, as well as previously identified regulators of asymmetric cell division. In this way, I will utilize the neural rosettes system to screen for new regulators of self-renewal and differentiation and examine the role of asymmetric cell division in human cortical development.
Original text from CORDIS.
Participants
- INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH · WienCoordinatorAustria
Links
Data: CORDIS, © European Union