The role of the stem cell regulator tatsf1 in mouse and human brain development

• Applicant: Dr. Nina Stephanie Corsini
• Subject Area: Developmental Neurobiology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 253283565

Stem cells are characterized by their unique abilities to self-renew and to differentiate. Both, self-renewal and differentiation need to be tightly controlled, as failure to do so can have severe consequences. Shifting the balance in this system towards proliferation can result in tumor formation whereas shifting the balance in favor of differentiation can result in stem cell loss and disease. It is thus crucial to identify factors governing the balance between differentiation and proliferation in the different stem cell compartments. Tatsf1 was identified as such a factor in a screen looking for proliferation and differentiation of neuronal stem cells in the drosophila larval brain. We have developed a mouse model to study tatsf1 function in a mammalian system. Our results indicate that tatsf1 is essential for embryonic stem cell proliferation and differentiation. Further, loss of tatsf1 results in decreased generation of neural tissue from embryonic stem cells. Tasf1 functions in a complex with members of the transcription and splicing machinery, which has been implicated in a human neurodevelopmental disease characterized by severely reduced brain size called microcephaly. Our results suggest that tatsf1 could perform an important function in mouse and human neural stem cells and brain development. I propose to study tatsf1 function in mouse and human neuronal development in vivo and in a novel 3D culture system called human cerebral organoids respectively. This combination will allow us to understand the role of tatsf1 in mammalian neuronal development and give us important insight into conservations of neurodevelopmental mechanisms between different species. Combining studies in the mouse with studies in human cerebral organoids will also help us to draw conclusions about the conservation of neurodevelopmental mechanisms between different species and it will give important information about the genesis of human neurodevelopmental disorders like microcephaly.

• DFG Programme: Research Fellowships
• International Connection: Austria
• Host: Professor Dr. Jürgen Knoblich