Neural circuit formation during development is fundamentally important for brain functions and requires precise regulation of many cellular processes, including neuronal migration, axon targeting, and synapse formation. Miswiring of neural networks underlies many neurological and psychiatric disorders, including intellectual and learning deficits, autism, addiction, and neurodegeneration. Our research aims to understand temporal and spatial regulation of cell signaling that ensures the accuracy of neuronal connections. The main questions we are pursuing include 1) how is cell signaling dynamically controlled as neurons/axons navigate through environs and 2) how alterations in neural circuitry contribute to disorders such as autism and drug addiction. We utilize a variety of approaches, including genetic mouse models, imaging, molecular and biochemical studies, and behavioral assays to address our questions.
Selected Publications (For a full list go to https://www.ncbi.nlm.nih.gov/myncbi/1FYWhcBWZ-B5x/bibliography/public/):
- Johnson V, Junge HJ, Chen Z. Temporal regulation of axonal repulsion by alternative splicing of a conserved microexon in mammalian Robo1 and Robo2. eLife 2019;8:e46042.
- Zhang C, Lai MB, Pedler M, Johnson V, Adams RH, Petrash JM, Chen Z, Junge HJ. Endothelial cell-specific inactivation of TSPAN12 reveals pathological consequences of blood-retina barrier defects in an otherwise intact vasculature. Arterioscler Thromb Vasc Biol. 2018;38(11), 2691-2705.
- Chen Z. Common cues wire the spinal cord: axon guidance molecules that regulate spinal neuron migration. Semin Cell Dev Biol. 2019;85:71-77.
- Zhang C, Lai MB, Khandan L, Chen Z, Junge HJ. Norrin-induced Frizzled4 endocytosis and endo-lysosomal trafficking control retinal angiogenesis and barrier function. Nat Commun. 2017 Jul 4;8:16050.
- Lai MB, Zhang C, Shi J, Johnson V, Khandan L, McVey J, Klymkowsky MW, Chen Z, Junge HJ. TSPAN12 is a Norrin co-receptor that amplifies Frizzled4 ligand selectivity and signaling. Cell Rep. 2017;19(13):2809-2822.
- Junge HJ, Yung AR, Goodrich LV, Chen, Z. Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord. Neural Dev. 2016 Oct 26;11(1):19.
- Leggere JC, Saito Y, Darnell RB, Tessier-Lavigne M, Junge HJ, Chen Z. NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord. Elife. 2016 May 25;5. pii: e14264.
- Saito Y, Miranda-Rottmann S, Ruggiu M, Park CY, Fak JJ, Zhong R, Duncan JS, Fabella BA, Junge HJ, Chen Z, Araya R, Fritzsch B, Hudspeth AJ, Darnell RB. NOVA2-mediated RNA regulation is required for axonal pathfinding during development. Elife. 2016 May 25;5. pii: e14371.
- Johnson V, Xiang M, Chen Z, Junge HJ. Neurite mistargeting and inverse order of intraretinal vascular plexus formation precede subretinal vascularization in VLDLR mutant mice. PLoS One. 2015 Jul 15;10(7):e0132013.