Sijun Zhu, MD, PhD

In my lab, we are particularly interested in the genetic control of the maintenance of neural stem cells (NSCs) and the generation of intermediate neural progenitor (INP). These two cell populations produce the diverse types of neurons and glia needed for the proper formation and homeostasis of the nervous system. NSCs self-renew to maintain their own population and they also produce the transient amplifying INP, which boosts the production of neurons and glia. Defects in NSC self-renewal or the generation of INP cells can lead to neurodevelopmental disorders or neurodegenerative diseases, whereas unrestricted proliferation of NSCs or INP cells can result in brain tumor formation. Deciphering how NSCs maintain self-renewal and produce INP cells will not only help us understand pathogenesis of neurodevelopmental disorders or brain tumor formation, but may also provide important information for designing new strategies to induce NSCs to produce neurons for brain repair. However, the underlying mechanisms that regulate NSC self-renewal and the generation of INP cells are still not well understood. In my lab, we study the recently identified type II neuroblasts (NBs, the Drosophila NSCs) in Drosophila larval brains as a model system. The Drosophila type II NBs produce neurons indirectly by generating transient amplifying INP cells like mammalian NSCs, thus provide a nice model system for studying neural stem cell self-renewal and the generation of INP cells. Our research goals are to uncover the gene regulatory network that control NSC self-renewal and INP production and to understand how dis-regulation of the gene regulatory network may lead to brain tumor formation using various genetic, molecular and cell biological, and approaches.

Selected Publications

1. Zhu S.¹*, Wildonger J.*, Barshow S.*, Younger S., Huang Y., Lee T. (2012). The bHLH Repressor Deadpan Regulates the Self-renewal and Specification of Drosophila Larval Neural Stem Cells Independently of Notch. PLoS ONE 7(10):e46724 (1. corresponding author; *, equal contribution)

2. Zhu S., Barshow S., Wildonger J., Jan L.Y., Jan Y.N. (2011). The Ets transcription factor Pointed promotes the generation of intermediate neural progenitors in Drosophila larval brains. PNAS 108(51):20615-20

3. Han C., Wang D., Soba P., Zhu S., Lin X., Jan L.Y., Jan Y.N. (2011). Integrins Regulate Repulsion-mediated Dendritic Patterning of Drosophila Sensory Neurons by Restricting Dendrites in a Two-dimensional Space. Neuron 73(1):64-78

4. Soba P.*, Zhu S.*, Emoto K., Younger S., Yang S.J., Yu H.H., Lee T., Jan L.Y., Jan Y.N. (2007). Drosophila sensory neurons require Dscam for dendritic self-avoidance and proper dendritic field organization. Neuron 54: 403-416 (*, equal contribution)

5. Zhu S., Lin S., Kao C.-F., Awasaki T, Chiang A.-S., and Lee T. (2006). Gradients of the Drosophila Chinmo BTB-Zinc finger protein govern neuronal temporal identity. Cell 127: 409-422

6. Kuo C., Zhu S., Younger S., Jan L.Y., Jan Y.N. (2006). Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning. Neuron 51:1-8

7. Zhu S., Perez R., Pen M., Lee T. (2005). Requirement of Cul3 for axonal arborization and dendritic elaboration in Drosophila mushroom body neurons. J Neurosci 25, 4189-4197

8. Zhu S., Chiang A.-S., Lee T. (2003). Development of the Drosophila mushroom bodies: elaboration, remodeling and spatial organization of dendrites in the calyx. Development 130, 2603-2610

9. Zhu S., Li H., Wang, Y.L., Xiao Z.J., Vinhko P., Piao Y.S. (2002). Retinoic acids promote the action of aromatase and 17b-hydroxysteroid dehydrogenase type1 on the biosynthesis of 17b-estradiol in placental cells. J Endocrinology 172, 31-43