601D Life Sciences Center
Understanding the mechanisms that govern nervous system patterning is a central focus of developmental neurobiology and, importantly, will result in the identification of molecular mechanisms relevant to many disease processes. The elaborate and precise patterns of neuronal connections in the mammalian central nervous system (CNS) established during development depend critically upon a vast number of extrinsic molecular cues. During development, neurons form connections with their appropriate targets by extending processes called axons and dendrites, which ultimately shape their diverse morphologies. The establishment of neuronal morphology is crucial for proper neural circuit formation, which enable complex behavior and cognitive function. However, the mechanisms by which axons select their correct pathways, find their targets, and form proper synaptic connections is not clearly understood. Moreover, the identity and mechanism that enables molecular cues to control the development of neuronal morphology and synaptic connections that collectively comprise the neural circuitry underlying complex cognitive function is poorly understood. Our overarching goal is to better understand how molecular cues regulate neuronal morphogenesis, synapse development and enable complex behavior, by combining interdisciplinary approaches from molecular and cellular biology, physiology, and behavior analysis.
The wiring of neuronal circuits in the mammalian CNS requires the precise formation and subsequent refinement of synapses during postnatal development. The vast majority of excitatory synapses in the mammalian CNS are formed on dendritic spines, tiny protrusions extended from the dendritic membrane. The morphology of the dendritic arbor and distribution of spines are critical determinants of correct circuit function. Although a number of molecular cues are known to promote spine and synapse number, little is known about the molecules that negatively regulate these events. Furthermore, the identity of molecular cues that control spine distribution along dendrites and synaptic structure remain to be defined.
In this regard, we are asking the following questions: 1) what are the molecules controlling neural circuit formation? 2) how are these connections maintained throughout life? 3) what are the underlying cellular mechanisms controlling axonal guidance versus synapse formation? To address these questions, we will employ cellular, molecular, and genetic approaches to analyze both the central and peripheral arms of the mouse nervous system. Our primary experimental approach is to use dissociated, cultured neurons from the developing neocortex as a model system. The formation of individual synapses in these cultures is studied using the following approaches. First, we use histological and immunocytochemical approaches to identify key molecules involved in the establishment of synaptic contacts in developing cortical neurons. Second, the sequence of molecular events that occur during synapse formation and maturation is investigated by live imaging changes in distribution of pre- and postsynaptic proteins fused to GFP and fluorescent calcium sensors (GCaMP sensors) to image neuronal activity. Finally, the molecular signals that may guide synapse formation are studied by manipulating them at forming synapses with pharmacological agents, transgenic technology and/or transfection techniques. Taken together, results from our work will provide a platform to study complex neural network formation and further our understanding of the establishment of neuronal circuitry, and how defects in these connections may lead to development of neurological disorders.
Recent courses taught:
2016 - present (spring): Introduction to Neuroanatomy: Structure and Function (21:120:404, Undergrad); Course Director.
2019 (fall): Topics in Biology: Neurodevelopment (26:120:616, Grad); Course Director.
2018 (fall): Cell Biology (21:120:355, Undergrad); Co-course Instructor.
B.S. in Physiological Sciences/Neuroscience, University of California, Los Angeles, 1998.
Ph.D. in Molecular, Cellular and Integrative Physiology, University of California, Los Angeles, 2003.
Assous, M, Martinez, E, Eisenberg, C, Shah, F, Kosc, A, Varghese, K, Espinoza, D, Bhimani, S, Tepper, JM, Shiflett, MW, Tran, TS. (2019). Neuropilin 2 Signaling Mediates Corticostriatal Transmission, Spine Maintenance, and Goal-Directed Learning in Mice. J Neurosci. 39:8845-8859. doi: 10.1523/JNEUROSCI.1006-19.2019.
Kung F, Wang, W, Tran, TS, Townes-Anderson, E. (2017). Sema3A Reduces Sprouting of Adult Rod Photoreceptors In Vitro. Invest Opthalmol Vis Sci. 58:4318-4331. doi: 10.1167/iovs.16-21075.
Shiflett, MW, Martinez, E, Khdour, H, Tran, TS. (2017). Functions of Neuropilins in Wiring the Nervous System and Their Role in Neurological Disorders. In: The Neuropilins: Role and Function in Health and Disease. Neufeld G, Kessler O, editors. Switzerland: Springer Nature; Chapter 8; p.125-149.
Peng, SS, Tran, TS. (2017). Regulation of Cortical Dendrite Morphology and Spine Organization by Secreted Semaphorins: A Primary Culture Approach. Methods Mol Biol. 1493:209-222. doi: 10.1007/978-1-4939-6448-2_15.
Hernandez-Enriquez, B, Wu, Z, Martinez, E, Olsen, O, Kaprielian, Z, Maness, PF, Yoshida, Y, Tessier-Lavigne, M, Tran, TS. (2015). Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing. Genes Dev. 29:2617-2632. doi: 10.1101/gad.268086.115.
Martinez, E, Tran, TS. (2015). Vertebrate spinal commissural neurons: a model system for studying axon guidance beyond the midline. Wiley Interdiscip Rev Dev Biol. 4:283-297. doi: 10.1002/wdev.173.
Shiflett, MW, Gavin, M, Tran, TS. (2015). Altered hippocampal-dependent memory and motor function in neuropilin 2-deficient mice. Transl Psychiatry. 5:e521. doi: 10.1038/tp.2015.17.
Yu, S, Yehia, G, Wang, J, Stypulkowski, E, Sakamori, R, Jiang, P, Hernandez-Enriquez, B, Tran, TS, Bonder, EM, Guo, W, Gao, N. (2014). Global ablation of the mouse Rab11a gene impairs early embryogenesis and matrix metalloproteinase secretion. J Biol Chem. 289:32030-32043. doi: 10.1074/jbc.M113.538223.
Demyanenko, GP, Mohan, V, Zhang, X, Brennaman, LH, Dharbal, KE, Tran, TS, Manis, PB, Maness, PF. (2014). Neural cell adhesion molecule NrCAM regulates Semaphorin 3F-induced dendritic spine remodeling. J Neurosci. 34:11274-11287. doi: 10.1523/JNEUROSCI.1774-14.2014.
Mlechkovich, G, Peng, SS, Shacham, V, Martinez, E, Gokhaman, I, Minis, A, *Tran, TS, *Yaron, A. (2014). Distinct cytoplasmic domains in Plexin-A4 mediate diverse responses to semaphorin 3A in developing mammalian neurons. Sci. Signal. 7:ra24. doi: 10.1126/scisignal.2004734. (*co-corresponding authors)
*#Tran, TS, *Carlin, E, Lin, R, Martinez, E, Johnson, JE, #Kaprielian, Z. (2013). Neuropilin 2 regulates the guidance of post-crossing spinal commissural axons in a subtype-specific manner. Neural Dev. 8:15. doi: 10.1186/1749-8104-8-15. (*co-first and #co-corresponding authors)
Calderon de Anda, F, Rosario, AL, Durak, O, Tran, T, Graff, J, Meletis, K, Rei, D, Soda, T, Madabhushi, R, Ginty, DD, Kolodkin, AL, Tsai, L. (2012). Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex. Nat. Neurosci. 15: 1022-31. doi: 10.1038/nn.3141.
Becker, PM, Tran, TS, Delannoy, MJ, He, CX, Shannon, JM, McGrath-Morrow, S. (2011). Semaphorin 3A contributes to distal pulmonary epithelial cell differentiation and lung morphogenesis. PLoS One 6. doi: 10.1371/journal.pone.0027449.
Demyanenko, GP, Riday, TT, Tran, TS, Dalal, J, Darnell, EP, Brennaman, LH, Sakurai, T, Grumet, M, Philpot, BD, Maness, PF. (2011). NrCAM deletion causes topographic mistargeting of thalamocortical axons to the visual cortex and disrupts visual acuity. J. Neurosci. 31:1545-1558. doi: 10.1523/JNEUROSCI.4467-10.2011.
Tran, TS, Rubio, ME, Clem, RL, Johnson, D, Case, L, Tessier-Lavigne, M, Huganir, RL, Ginty, DD and Kolodkin, AL. (2009). Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS. Nature, 462:1065-1069. doi: 10.1038/nature08628.
Kolk, SM, Gunput, RF, Tran, TS, van den Heuvel, DMA, Prasad, AA, Hellemons, AJGM, Adolfs, Y, Ginty, DD, Kolodkin, AL, Burbach, PH, Smidt, MP, Pasterkamp, RJ. (2009). Semaphorin 3F is a bifunctional guidance cue for dopaminergic axons and controls their fasciculation, channeling, rostral growth and intracortical targeting. J. Neurosci. 29:12542-12557. doi: 10.1523/JNEUROSCI.2521-09.2009.
Wright, AG, Demyanenko, GP, Powell, A, Schachner, M, Enriquez-Barreto L, Tran, TS, Polleux, F, and Maness, PF. (2007). Close Homolog of L1 and Neuropilin 1 mediate guidance of thalamocortical axons at the ventral telencephalon. J. Neurosci. 27:13667- 13679. doi: 10.1523/JNEUROSCI.2888-07.2007.
Tran, TS, Kolodkin, AL, and Bharadwaj, R. (2007). Semaphorin regulation of cellular morphology. Ann. Rev. Cell Dev. Biol. 23:263-292. doi: 10.1146/annurev.cellbio.22.010605.093554.
Hoe, H-S, Tran, TS, Matsuoka, Y, Howell, BW and Rebeck, GW. (2006). DAB1 and Reelin effects on amyloid precursor protein and ApoE receptor 2 trafficking and processing. J. Biol. Chem. 281:35176-35185. doi: 10.1074/jbc.M602162200.
Huber, AB, Kania, A, Tran, TS, Gu, C, De Marco Garcia, N, Lieberam, I, Johnson, D, Jessell, TM, Ginty, DD and Kolodkin, AL. (2005). Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. Neuron, 48:949-964. doi: 10.106/j.neuron.2005.12.003.
Chen, K, Ochalski, PG, Tran, TS, Sahir, N, Schubert, M, Pramatarova, A and Howell, BW. (2004). Interaction between Dab1 and CrkII is promoted by Reelin signaling. J. Cell Sci. 117:4527-36.
Tran, TS and Phelps, PE. (2004). Embryonic GABAergic spinal commissural neurons project rostrally to mesencephalic targets. J. Comp. Neurol. 475:327-339.
Tran, TS, Alijani, A and Phelps, PE. (2003). Unique developmental patterns of GABAergic neurons in rat spinal cord. J. Comp. Neurol. 456:112-126.
Tran, TS and Phelps, PE. (2000). Axons crossing in the ventral commissure express L1 and GAD65 in developing rat spinal cord. Dev. Neurosci. 22:228-236.
Phelps, PE, Alijani, A and Tran, TS. (1999). Ventrally located commissural neurons express the GABAergic phenotype in developing rat spinal cord. J. Comp. Neurol. 409:285-298.
Faculty advisor for majors in:
Clinical Laboratory Sciences
Medical Imaging Sciences