Presenter: Patrick Johnson
Faculty Mentor: Sen-Lin Lai, Chris Q. Doe
Presentation Type: Oral
Primary Research Area: Science
Major: Math, Biology
Funding Source: HHMI; SPUR
Proper neural development requires a fine balance between neural stem cell self-renewal and quiescence. Tumorigenesis occurs when stem cells over-proliferate, and early onset of quiescence leads to insufficient progeny and impaired brain development. Prospero, a conserved transcription factor, is expressed in neuroblasts (neural stem cells in Drosophila), but must be excluded from the nucleus to permit self-renewal. Transient import of low-level Prospero into the neuroblast nucleus results in termination of the cell cycle and induces quiescence. The cellular components aiding in nuclear exclusion of Prospero, and thereby preventing premature quiescence, have not been identified. We found that the nucleolus gene nucleostemin 3 (NS3) is required for neuroblast self-renewal. The knock down of NS3 does not change the number of neuroblasts in the brain, but significantly reduces the number
of neuroblasts in the cell cycle. Additionally, Prospero was localized in the nucleus and the proliferating neuroblast marker Worniu was suppressed. These phenotypes (cell cycle arrest, nuclear Prospero, and suppression of Worniu) are the features of quiescent neuroblasts; we thus conclude that NS3 is required for neuroblast self-renewal and the loss of NS3 results in premature quiescence. Further characterization has similarly identified specific nuclear transport genes as being necessary for neuroblast self-renewal. Together, these finding help identify a necessary pathway through which neural stem cells regulate the balance between quiescence and self-renewal