725 N. Wolfe Street
Baltimore MD 21205
Our research is focused on understanding how neuronal connectivity is established during development. Our work investigates the function of extrinsic guidance cues and their receptors on axonal guidance, dendritic morphology, and synapse formation and function. For several years we have investigated how neural circuits are formed and maintained through the action of guidance cues that include semaphorin proteins, their classical plexin and neuropilin receptors, and also novel receptors. We employ a cross phylogenetic approach, using both invertebrate and vertebrate model systems, to understand how guidance cues regulate neuronal pathfinding, morphology, and synaptogenesis. We also seek to understand how these signals are transduced to cytosolic effectors. Though broad in scope, our interrogation of the roles played by semaphorin guidance cues provides insight into the regulation of neural circuit assembly and function. As a result of the ongoing projects in my laboratory, I and my colleagues have extensive experience in both mouse and fly genetic manipulations and neuroanatomical analysis. Our current work includes understanding the origins of laminar organization in the CNS. This direction has resulted in our identification of guidance cues and recpetors that regulate both specific and general aspects of neurite stratification in the mouse retina, in addition to the targeting of retinal ganglion cell axons to retinorecipient midbrain targets. We are also exploring how distinct circuits that regulate directional motion tuning responses in mammals are assembled and function. Our work in the mouse retina has prompted us to look for cellular and molecular mechanisms that regulate laminar organization in the mouse neocortex. Taken together, these studies seek to understand the molecular basis of neural circuit assembly and how this impacts behavioral responses to sensory input.
Al-Khindi, T., Sherman, M., Gopal, P., Pan, Z., Kodama, T., Kiraly, J., Zhang, H., Goff, L.A., Du Lac, S., and Kolodkin, A.L. (2022). The transcription factor Tbx5 specifies direction-selective ganglion cell fate. Current Biology, 32, 4286-4298.
Hunyara, J.L., Foshe, S., Varadaragan, S.G., Gribble, K.D., Huberman, A.D., and Kolodkin, A.L. Characterization of non-alpha retinal ganglion cell injury responses reveals a possible block to restoring ipRGC function. (2022). Exp. Neurol. 357, 114176 [PMCID PMC9549754].
Peng, Y-R.**, James-Esposito**, R.E., Yan, W., Kay, J.N., Kolodkin, A.L.*, Sanes, J.R.* (2020). Binary fate choice between closely related interneuronal types is determined by a Fezf1-dependent postmitotic transcriptional switch. Neuron, 105, 464-474 (*co-corresponding authors; **co-first authors).
Xie, X., Tabuchi, M., Corver, A., Duan, G., Wu, M.N., and Kolodkin, A.L. (2019) Semaphorin-2b regulates sleep circuit formation in the Drosophila central brain. Neuron, 104, 322-337.
Wang, Q., Chiu, S.-L., Koropouli, E., Hong, I., Mitchell, S., Gustina, A.S., Zhu, Q., Ginty, D., Huganir, R.L.,and Kolodkin, A.L. (2017). Neuropilin-2/PplexA3 receptors associate with GluA1 and mediate Sema3F-dependent homeostatic scaling in cortical neurons. Neuron, 96, 1084-1098.
Jeong, S., Yang, D-s., Hong, Y.G., Mitchell, S.P., Brown, M.P., and Kolodkin, A.L. (2017). Varicose and cheerio collaborate with pebble to mediate semaphorin-1a reverse signaling in Drosophila. PNAS, 114, E8245-E8326.
Xie, X., Tabuchi, M., Brown, M.P., Mitchell, S.P., Wu, M.N., and Kolodkin, A.L. (2017). The laminar organization of the Drosophila ellipsoid body is semaphorin-dependent and prevents the formation of ectopic synaptic connections. eLife, 6:e25328, DOI: 10.7554/eLife.25328.
Hand, R.A., Khalid, S., Tam, E., and Kolodkin, A.L. (2015). Axon dynamics during neocortical laminar innervation, Cell Reports, 12, 172-182.
Sun, L.O., Brady, C.M., Cahill, H., Sakuta, Dhande, O.S., Noda, M., Huberman, A.D., Nathans, J., Kolodkin, A.L. (2015). Functional assembly of accessary optic system circuitry critical for compensatory eye movements. Neuron. 86, 971-984.
Riccomagno, M.M., Sun, L.O., Brady, C.M., Alexandropoulos, K., Seo, S., Kurokawa, M., and Kolodkin, A.L. (2014). Cas adaptor proteins organize the retinal ganglion cell layer downstream of integrin signaling. Neuron, 81, 779-786.
Sun, L.O., Jiang, Z., Rivlin-Etzion, M., Hand, R., Brady, C.M., Matsuoka, R.L., Yau, K.-W., Feller, M. B., and Kolodkin, A.L. (2013). On and Off retinal circuit assembly by divergent molecular mechanisms. Science, 342, 1241947; DOI:10.1126/science.1241974.
Jeong, S., Juhaszova, K., and Kolodkin, A.L. (2012). The control of semaphorin-1a-mediated reverse signaling by opposing pebble and RhoGAPp190 functions in Drosophila. Neuron, 140, 627-38.
Riccomagno, M, Hurtado, A., Wang, H.-B., Macopson, J.G.J., Griner, E.M., Betz, A., Brose, N. Kazanietz, M.G., and Kolodkin, A.L. (2012). The RacGAP b-Chimaerin selectively mediates stereotyped hippocampal axon pruning. Cell, 149, 1594-1606.
Lloyd, T.E., Machamer, J., O’Hara, K, Kim, J.H., Collins, S.E., Wong, M.Y., Sahin, B., Imlach, W., Yang, Y., Levitan, E.S., McCabe, B.D. and Kolodkin, A.L. (2012). The p150/Glued CAP-Gly domain regulates initiation of retrograde transport at synaptic termini. Neuron, 74, 344-360.
Matsuoka, R.L., Chivatakarn, O, Badea, T.C., Samuels, I.S., Cahill, H., Katayama K, Suto F, Chédotal, A., Peachey, N.S., Nathans, J, Yoshida, Y., Giger, R.J., and Kolodkin, A.L. (2011). Class5 transmembrane semaphorins control mammalian inner retinal lamination, neurite arborization, and function. Neuron 71, 460-473.
Matsuoka, R.L., Nguyen-Ba-Charvet, K.T., Parray, A., Badea, T.C., Chedotal, A., and Kolodkin, A.L. (2011). Transmembrane semaphorin signaling controls laminar stratification in the mammalian retina. Nature, 470, 259-263.
Wu, Z., Sweeney, L.B. Ayoob, J.C., Chak, K., Andreone, B.J., Ohyama,T. Kerr, R., Luo, L, Zlatic, M., and Kolodkin, A.L. (2011). A combinatorial semaphorin code instructs the initial steps of sensory circuit assembly in the Drosophila CNS. Neuron, 70, 281-298.
Tran, T.S., Rubio, M.E., Clem, R.L., Johnson, D.,Case, L.C., Tessier-Lavigne, M., Huganir, R.L., Ginty, D.D., and Kolodkin, A.L. (2009). Secreted Semaphorins Control Spine Distribution and Morphogenesis in the Postnatal CNS. Nature, 462, 1065-1069.
Huber, A.B., Kania, A., Tran, T.S., Gu, C., De Marco Garcia, N., Lieberam, I., Johnson, D., Jessell, T.M. Ginty, D.D., and Kolodkin, A.L. (2005). Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. Neuron, 48, 949-964.
Kantor, D.B., Chivatakarn, O., Peer, K.L., Oster, S.F., Inatani, M., Hansen, M.J., Flanagan, J.G., Yamaguchi, Y., Sretavan, D.W., Giger, R.J., and Kolodkin, A.L. (2004). Semaphorin 5A is a Bifunctional Axon Guidance Cue Regulated by Heparan and Chondroitin Sulfate Proteoglycans. Neuron, 44, 961-975.
Terman, J.R., and Kolodkin, A.L. (2004). The AKAP Nervy direction couples Protein Kinase A to Plexin-mediated semaphorin repulsion. Science, 303, 1204-1207.
Pasterkamp, R.J., Peshon, J.J., Spriggs, M.K. and Kolodkin, A.L. (2003). Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature, 424, 398-405.
Giger, R.J., Urquhart, E.R., Gillespie, S.K.H., Levengood, D.V., Ginty, D.D., and Kolodkin, A.L. (1998). Neuropilin-2 is a receptor for semaphorin IV: Insight into the structural basis of receptor function and specificity. Neuron, 21, 1079-1092.
Yu, H.-H., Araj, H.H., Ralls, S.A., and Kolodkin, A.L. (1998). The transmembrane semaphorin Sema-I is required in Drosophila for embryonic motor and CNS axon guidance. Neuron, 20, 207-220.
Kolodkin, A.L.*, Levengood, D.V., Rowe, E.G., Tai, Y.-T., Giger, R. J., and Ginty, D. D.* (1997). Neuropilin is a semaphorin III receptor. Cell, 90, 753-762 (*-co-corresponding authors).