Stem cells to synapses: regulation of self-renewal and differentiation in the nervous system
12 August 2011
|Stem cells to synapses: regulation of self-renewal and differentiation in the nervous system|
The School of Biological Sciences proudly presents a seminar from visiting Cambridge molecular biologist, Professor Andrea Brand
Discovering how stem cells are maintained in a multipotent state and how their progeny differentiate into distinct cellular fates is a key step in the therapeutic use of stem cells to repair tissues after damage or disease. We are investigating the genetic networks that regulate neural stem cells in Drosophila. Stem cells can divide symmetrically to expand the stem cell pool, or asymmetrically to self-renew and generate a daughter cell destined for differentiation. The balance between symmetric and asymmetric division is critical for the generation and repair of tissues, as unregulated stem cell division results in tumourous overgrowth. Symmetrically dividing stem cells exist in the optic lobe of the brain, where they convert to asymmetrically dividing neuroblasts. By comparing the transcriptional profiles of symmetrically and asymmetrically dividing stem cells, we identified Notch as a key regulator of the switch from symmetric to asymmetric division. During asymmetric division cell fate determinants, such as the homeodomain transcription factor Prospero, are partitioned from the neural stem cell to its daughter. By identifying Prospero's targets throughout the genome we showed that Prospero represses genes for self-renewal and activates differentiation genes. In prospero mutants, differentiating daughters revert to a stem cell-like fate: they express markers of self-renewal, continue to proliferate, fail to differentiate and generate tumours.
The systemic regulation of stem cells ensures they meet the needs of the organism during growth, and in response to injury. A key point of regulation is the decision between quiescence and proliferation. During development, Drosophila neural stem cells transit through a period of quiescence separating distinct embryonic and post-embryonic phases of proliferation. Neuroblasts exit quiescence in response to a nutrition-dependent signal from the fat body. We identified a population of glial cells that produce Insulin/IGF-like peptides in response to nutrition, and show that the Insulin/IGF Receptor pathway is necessary for neuroblasts to exit quiescence.
Time: 1pm - 2pm
Location: New Law School Lecture Theatre 101, New Law School, The University of Sydney
Contact: Carla Avolio