Sijun Zhu profile picture
315 464-7731

Sijun Zhu, MD, PhD

4611 Institute For Human Performance (IHP)
505 Irving Avenue
Syracuse, NY 13210
Sijun Zhu's email address generated as an image


Associate Professor of Neuroscience and Physiology




Biomedical Sciences Program
Neuroscience and Physiology
Neuroscience Program


Genetic mechanisms of Drosophila neural stem cell specification and sub-cellular specific targeting of dendrites.


Postdoctoral Fellow: University of California at San Francisco, 2012
PhD: University of Illinois at Urbana-Champaign, 2005, Developmental Neurobiology



Our lab is interested in elucidating cellular and molecular mechanisms that regulate brain development using Drosophila as a model organism. Specifically, we are working on the following two lines of research using various powerful genetic, genomic, molecular biological, biochemical and confocal imaging approaches.

1) Genetic mechanisms that control the generation of brain complexity and brain tumor formation. The increased brain complexity is believed to be responsible for higher intellectual ability in humans. Generating brain complexity requires the maintenance of neural stem cells (NSCs) and the production of intermediate neural progenitor cells (INPs), transient amplification of which is critical for boosting the number of neurons and glia generated from NSCs. However, aberrant proliferation or defects in differentiation of NSCs and INPs can lead to brain tumor formation. Drosophila type II neuroblasts (NBs, Drosophila NSCs) remarkably resemble mammalian NSCs. They can not only maintain their own population through self-renewal but also produce large amount of neurons by generating transient amplifying INPs. Furthermore, type II NB lineages are extremely susceptible to tumorigenesis because INPs are genetically unstable and prone to dedifferentiation (Fig.1). Thus, type II NB lineages provide an excellent model for studying the generation of brain complexity and the formation of brain tumors. The major goal of this line of research is to dissect genetic mechanisms that control the specification/self-renewal of type II NBs and differentiation/dedifferentiation of INPs in the developing Drosophila brain at both the transcriptional and post-transcriptional levels.



Fig. 1. (A-A') A normal type II NB lineage labeled with GFP (A) and schematic diagrams of the lineage and its neurogenesis pattern (A'). (B-') A type II NB lineage with premature differentiation of INPs. (C-C') A type II NB lineage with defects in INP differentiation.

2) Cellular and molecular mechanisms that control neural circuit formation at the subcellular level in the Drosophila central brain. One of the fundamental questions in developmental neurobiology is how neurons form subcellular specific synaptic contacts. Subcellular-specificity of synaptic connections has a profound impact on neuronal activity and behavior output. In the Drosophila learning and memory center, the mushroom body, mushroom body output neurons (MBONs) target their dendrites to specific subcellular locations (or called compartments) of the mushroom body axons to form synaptic contacts. A total of 34 MBONs of 21 types elaborate their dendrites in 16 compartments that together tile the five MB axonal lobes without overlap (Fig. 2). We use the mushroom body output neurons as a novel model system to investigate cellular and molecular mechanisms that govern the compartment-specific targeting and tiling of dendrites in the central brain of Drosophila.



Fig. 2. (A) A diagram of the Drosophila mushroom body and its five axonal lobes. (B) A diagram of 16 compartments on 5 mushroom axonal lobes. Targeting of MBON dendrites to a2 and a’2 compartments is indicated (adapted from Aso et al., 2014). (C) Two MBONs labeled in green and red target their dendrites to the γ5 and γ4 compartments without overlapping with each other in the mushroom body axonal lobes (in blue). (D) MBON dendrites labeled with alternative fluorescent colors tile four neighboring compartments (γ2 through γ5) of the mushroom body γ lobe.


Manuscripts in submission

Connell M, Xie Y, Chen R, Zhu S. Kin17 drives dissociation of Mira from the centrosome in neuroblasts by regulating splicing of Flfl. bioRxiv 2021.11.03.467193; doi: (under revision at Cell Reports)

Selected Publications

Chen R, Deng X, Zhu S. The Ets protein Pointed P1 represses Asense expression in type II neuroblasts by activating Tailless. PLoS Genet. 2022 Jan;18(1):e1009928. doi: 10.1371/journal.pgen.1009928. eCollection 2022 Jan. PubMed PMID: 35100262; PubMed Central PMCID: PMC8830786.

Chen R, Hou Y, Connell M, Zhu S. Homeodomain protein Six4 prevents the generation of supernumerary Drosophila type II neuroblasts and premature differentiation of intermediate neural progenitors. PLoS Genet. 2021 Feb;17(2):e1009371. doi: 10.1371/journal.pgen.1009371. eCollection 2021 Feb. PubMed PMID: 33556050; PubMed Central PMCID: PMC7895384.

Zhu S, Chen R, Soba P, Jan YN. JNK signaling coordinates with ecdysone signaling to promote pruning of Drosophila sensory neuron dendrites. Development. 2019 Apr 17;146(8). doi: 10.1242/dev.163592. PubMed PMID: 30936183; PubMed Central PMCID: PMC6503988.

Rode S, Ohm H, Anhäuser L, Wagner M, Rosing M, Deng X, Sin O, Leidel SA, Storkebaum E, Rentmeister A, Zhu S, Rumpf S. Differential Requirement for Translation Initiation Factor Pathways during Ecdysone-Dependent Neuronal Remodeling in Drosophila. Cell Rep. 2018 Aug 28;24(9):2287-2299.e4. doi: 10.1016/j.celrep.2018.07.074. PubMed PMID: 30157424.

Li X, Chen R, Zhu S. bHLH-O proteins balance the self-renewal and differentiation of Drosophila neural stem cells by regulating Earmuff expression. Dev Biol. 2017 Nov 15;431(2):239-251. doi: 10.1016/j.ydbio.2017.09.011. Epub 2017 Sep 9. PubMed PMID: 28899667; PubMed Central PMCID: PMC5658246.

Xie Y, Li X, Deng X, Hou Y, O'Hara K, Urso A, Peng Y, Chen L, Zhu S. The Ets protein Pointed prevents both premature differentiation and dedifferentiation of Drosophila intermediate neural progenitors. Development. 2016 Sep 1;143(17):3109-18. doi: 10.1242/dev.137281. Epub 2016 Aug 10. PMID:27510969

Li X, Xie Y, Zhu S. Notch maintains Drosophila type II neuroblasts by suppressing expression of the Fez transcription factor Earmuff. Development. 2016 Jul 15;143(14):2511-21. doi: 10.1242/dev.136184. Epub 2016 May 5.PMID:27151950

Huang X, He Y, Dubuc AM, Hashizume R, Zhang W, Reimand J, Yang H, Wang TA, Stehbens SJ, Younger S, Barshow S, Zhu S, Cooper MK, Peacock J, Ramaswamy V, Garzia L, Wu X, Remke M, Forester CM, Kim CC, Weiss WA, James CD, Shuman MA, Bader GD, Mueller S, Taylor MD, Jan YN, Jan LY. EAG2 potassium channel with evolutionarily conserved function as a brain tumor target. Nat Neurosci. 2015 Sep;18(9):1236-46. doi: 10.1038/nn.4088. Epub 2015 Aug 10. PubMed PMID: 26258683; PubMed Central PMCID: PMC4639927.

Xie Y, Li X, Zhang X, Mei S, Li H, Urso A, Zhu S. The Drosophila Sp8 transcription factor Buttonhead prevents premature differentiation of intermediate neural progenitors. Elife. 2014 Oct 6;3. doi: 10.7554/eLife.03596.PMID:25285448

Han C, Wang D, Soba P, Zhu S, Lin X, Jan LY, Jan YN. Integrins regulate repulsion-mediated dendritic patterning of drosophila sensory neurons by restricting dendrites in a 2D space. Neuron. 2012 Jan 12;73(1):64-78. doi: 10.1016/j.neuron.2011.10.036.PMID:22243747

Zhu S, Barshow S, Wildonger J, Jan LY, Jan YN. Ets transcription factor Pointed promotes the generation of intermediate neural progenitors in Drosophila larval brains. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20615-20. doi: 10.1073/pnas.1118595109. Epub 2011 Dec 5.PMID:22143802

Soba P, Zhu S, Emoto K, Younger S, Yang SJ, Yu HH, Lee T, Jan LY, Jan YN. Drosophila sensory neurons require Dscam for dendritic self-avoidance and proper dendritic field organization. Neuron. 2007 May 3;54(3):403-16.PMID:17481394

Zhu S, Lin S, Kao CF, Awasaki T, Chiang AS, Lee T. Gradients of the Drosophila Chinmo BTB-zinc finger protein govern neuronal temporal identity. Cell. 2006 Oct 20;127(2):409-22.PMID:17055440

Kuo CT, Zhu S, Younger S, Jan LY, Jan YN. Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning. Neuron. 2006 Aug 3;51(3):283-90.PMID:16880123

Zhu S, Perez R, Pan M, Lee T. Requirement of Cul3 for axonal arborization and dendritic elaboration in Drosophila mushroom body neurons. J Neurosci. 2005 Apr 20;25(16):4189-97.PMID:15843622