There is a possibility that draxin-DCC initiates signaling event opposite to the netrin-DCC signaling. Hence, in the case of draxin-netrin-DCC interaction it would be interesting to investigate the status of two different intracellular signaling cascades simultaneously that normally switch on through DCC-netrin or DCC-netrin-UNC5 interactions. Several reports indicate that axonal outgrowth stimulating and turning activity of netrin-1 through its receptor DCC leads to inhibit RhoA, member of Rho GTPases family of intracellular proteins. Therefore, the first possibility is to check whether draxin inhibits axonal outgrowth by increasing the Rho kinase activity. Dissociated cortical neurons can be cultured in the presence or absence of specific inhibitor of Rho kinase Y27632 in control or draxin conditioned medium. Positive data from this experiment can be confirmed further by doing other experiments like IP assay to check the level of active Rho from draxin treated neurons, growth cone collapse assay to see whether Rho kinase inhibitor would rescue draxin activity.
56 Involvement of Ca+2 mediated cAMP level
The conclusion of some research findings (Hong, et al. 2000; Nishiyama, et al. 2003) suggest that at a high ratio of cAMP to cGMP, netrin-1 works as an attractant through its receptor DCC by enhancing the Ca+2 influx on the other hand, lower ratio of cAMP to cGMP reduces Ca+2 influx and thereby induces repulsion. So, draxin`s neurite outgrowth inhibitory and growth collapse response through DCC might lead lowering influx of Ca+2.
intracellularly. For this experiment, dissociated cortical neurons from wild type and DCC KO mice can be bath applied either with draxin-AP or control-AP conditioned medium and later calcium imaging can be performed using calcium indicator Fluo-4 (Invitrogen).
Results from this experiment would clarify whether the above signaling event associated with the level of Ca+2 influx occurs when the neurons are treated with draxin.
Bibilography
Adams, R., Wilkinson, G., Weiss, C., Diellia, F., Gale, N.W., et al. (1999). Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes and Dev. 13:295-306.
Augsburger, A., Schuchardt, A., Hoskins, S., Dodd, J. and Butler, S. (1999). BMPs as mediators of roof plate repulsion of commissural neurons. Neuron 24:127 -141.
Bagnard, D., Lohrum, M., Uziel, D., Puschel, A.W., and Bolz, J. (1998). Semaphorins act as attractive and repulsive guidance signal during the development of cortical projections. Development 125:5043-5053.
Barallobre, M.J., Del Rio, J.A., Alcantara, S., Borrell, V., Aguado, F., et al. (2000).
Aberrant development of hippocampal circuits and altered neural activity in netrin 1-deficient mice, Development 127:4797-4810.
Barallobre, M.J., Pascual, M., Del Rio J.A., and Soriano, E. (2005). The Netrin family of guidance factors: emphasis on Netrin-1 signaling. Brain Res. Rev. 49:22-47.
Battye, R., Stevens, A. and Jacobs, J.R. (1999). Axon repulsion from the midline of the Drosophila CNS requires slit function. Development 126:2475-81.
Behar, O., Golden, J.A., Mashimo, H., Schoen, F.J., and Fishman, M.C. (1996).
Semaphorin III is needed for normal patterning and growth of nerves, bones and heart.
Nature 383:525-528.
Bosley, T.M., Salih, M.A., Jen, J.C., Lin, D.D., Oystreck, D., et al. (2005). Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3.
Neurology 64:1196-203.
Braisted, J. E., Catalano, S.M., Stimac, R., Kennedy, T. E., Tessier-Lavigne, M., et al.
(2000). Netrin-1 promotes thalamic axon growth and is required for proper development
58
of the thalamocortical projection. J. Neurosci. 20:5792-5801.
Brose, K., Bland, K.S., Wang, K.H., Arnott, D., Henzel, W., et al. (1999). Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell 96:795-806.
Brose, K. and Tessier-Lavigne, M. (2000). Slit proteins: key regulators of axon guidance, axonal branching, and cell migration. Curr. Opin. Neurobiol. 10:95-102.
Butler, S.J. and Dodd, J. (2003). A role for BMP heterodimers in roof plate-mediated repulsion of commissural axons. Neuron 38:389-401.
Castellani, V., Chedotal, A., Schachner, M., Faivre-Sarrailh, C., and Rougon, G. (2000) Analysis of the L1-deficient mouse phenotype reveals crosstalk between sema 3A and L1 signaling pathways in axonal guidance. Neuron 27:237-249.
Chan, SS-Y., Zheng, H., Su, M-W., Wilk, R., et al. (1996). UNC-40, a C. elegans homolog of DCC (Deleted in colorectal cancer) is required in motile cells responding to UNC-6 netrin cues. Cell 87:87-95.
Charron, F., Stein, E., Jeong, J., McMahon, A.P. and Tessier-Lavigne, M. (2003). The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113:11-23.
Charron, F. and Tessier-Lavigne, M. (2005). Novel brain wiring functions for classical morphogens: a role as graded positional cues in axon guidance. Development 132:2251-2262.
Cheng, H-J, Bagri, A., Yaron, A., Stein, E., Pleasure, S.J., and Tessier-Lavigne, M.
(2001).
Plexin-A3 mediates semaphorin signaling and regulates the development of hippocampal axonal projections. Neuron 32:249-263.
Colamarino, S.A. and Tessier-Lavigne, M. (1995). The role of the floor plate in axon guidance. Annu. Rev. Neurosci. 18:497-529.
De Castro, F., Hu, L., Drabkin, H., Sotelo, C., and Chedotal, A. (1999). Chemoattraction and chemorepulsion of olfactory bulb axons by different secreted Semaphorins, J.
Neurosci. 19: 4428–4436.
Derer, P., Caviness Jr, V.S. and Sidman, R.L. (1977). Early cortical histogenesis in the primary olfactory cortex of the mouse. Brain Res. 123:27-40.
Dickson, B. J. (2002). Molecular mechanisms of axon guidance. Science 298:1959-1964.
Dickson, B.J. and Gilestro, G.F. (2006). Regulation of commissural axon pathfinding by Slit and its Robo receptors. Annu. Rev. Cell. Dev. Biol. 22:651-675
Fazeli, A., Dickinson, S.L., Hermiston, M.L., Tighe, R.V., Steen, R.G., et al. (1997).
Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene. Nature 386:796–804.
Feiner, L., Koppel, A. M., Kobayashi, H., and Raper, J. A. (1997). Secreted Chick Semaphorins Bind Recombinant Neuropilin with Similar Affinities but Bind Different Subsets of Neurons In Situ. Neuron 19:539-545.
Finger, J.H., Bronson, R.T., Harris, B., Johnson, K., Przyborski, S.A., and Ackerman, S.L. (2002). The netrin 1 receptors Unc5h3 and Dcc are necessary at multiple choice points for the guidance of corticospinal tract axons. J. Neurosci. 22:10346-10356.
Flanagan, J.G. and Cheng, H.J. (2000). Alkaline phosphatase fusion proteins for molecular characterization and cloning of receptors and their ligands. Methods Enzymology 327:198-210.
60
Fouquet, C., Di Meglio, T., Ma, L., Kawasaki, T., Long, H., et al. (2007). Robo1 and Robo2 control the development of the lateral olfactory tract. J. Neurosci. 27:3037-3045.
Gad, J.M., Keeling, S.L., Wilks, A.F., Tan, S. and Cooper, H.M. (1997). The expression patterns of guidance receptors, DCC and Neogenin, are spatially and temporally distinct throughout mouse embryogenesis. Dev. Biol. 192:258–273.
Giordano, S. Corso, S., Conorotto, P., Artigiani, S., Gilestro, G., et al. (2002). The semaphorin 4D controls invasive growth by coupling with Met. Nat. Cell Biol. 4:720-724.
Geisbrecht, B.V., Dowd, K.A., Barfield, R.W., Longo, P.A. and Leahy, D.J. (2003).
Netrin binds discrete subdomains of DCC and UNC5 and mediates interactions between DCC and Heparin. J. Biol. Chem. 278:32561-32568.
Hata, K., Fujitani, M., Yasuda, Y., Doya, H., Saito, T., et al. (2006). RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J. Cell. Biol. 173:47-58.
Hedgecock, E. M., Culotti, J. G. and Hall, D. H. (1990). The unc-5, unc-6,and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 4:61-85.
Holmberg, J., Clarke, D.L. and Frisen, J. (2000). Regulation of repulsion versus adhesion by different splice forms of an Eph receptor. Nature 408:203-206.
Holmes, G.P., Negus, K., Burridge, L., Raman, S., Algar, E., et al. (1998). Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis. Mech. Dev. 79:5-72
Hong, K., Hinck, L., Nishiyama, M., Poo, M. M., Tessier-Lavigne, M. et al. (1999). A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion. Cell 97:927-941.
Hong, K., Nishiyama, M., Henley, J., Tessier-Lavigne, M. and Poo, M. (2000). Calcium
signaling in the guidance of nerve growth by netrin-1. Nature 403:93-98.
Howitt, J.A., Clout, N.J., and Hohenester, E. (2004). Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit. EMBO J. 23:4406-12
Hu, H. (1999). Chemorepuslion of neuronal migration by Slit2 in the developing mammalian forebrain. Neuron 23:703-711.
Ingham, P. W. and McMahon, A. P. (2001). Hedgehog signaling in animal development:
paradigms and principles. Genes Dev. 15:3059-3087.
Islam, S.M., Shinmyo, Y., Okafuji, T., Su, Y., Naser, I.B., et al. (2009). Draxin, a repulsive guidance protein for spinal cord and forebrain commissures. Science 323, 388-393.
Ito, K., Kawasaki,T., Takashima, S., Matsuda, I., Aiba, A., et al. (2008). Semaphorin 3F confines ventral tangential migration of lateral olfactory tract neurons onto the telencephalon surface. J. Neurosci. 28:4414-4422.
Itoh, A., Miyabayashi, T., Ohno, M., Sakano, S. (1998). Cloning and expressions of three mammalian homologues of Drosophila slit suggest possible roles for Slit in the formation and maintenance of the nervous system. Brain Res. Mol. Brain Res. 62:175-86.
Jen, J.C., Chan, W.M., Bosley, T.M., Wan, J., Carr, J.R., et al. (2004). Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis.
Science 304:1509-13.
Jessell, T. M. (2000). Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat. Rev. Genet. 1:20-29.
Kawakami, A., Kitsukawa, T., Takagi, S. and Fujisawa, H. (1996). Developmentally regulated expression of a cell surface protein, neuropilin, in the mouse nervous system. J.
Neurobiol. 29:1-17
62
Kawasaki, T., Ito, K. and Hirata, T. (2006). Netrin 1 regulates ventral tangential migration of guidepost neurons in the lateral olfactory tract. Development 133:845–853
.
Kennedy, T. E., Serafini, T., de la Torre, J. R. and Tessier-Lavigne, M. (1994). Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord.
Cell 78:425-435.
Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E.D., Chan, S.-Y.S., et al. (1996).
Deleted in colorectal cancer (DCC) encodes a netrin receptor. Cell 87:175-185.
Kidd, T., Brose, K., Mitchell, K.J., Fetter, R.D., Tessier-Lavigne, M., et al. (1998).
Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell 92:205-15.
Kidd, T., Bland, K.S. and Goodman, C.S. (1999). Slit is the midline repellent for the robo receptor in Drosophila. Cell 96:785-94.
Kitsukawa, T., Shimizu, M., Sanbo, M., Hirata, T., Taniguchi, M., et al. (1997).
Neuropilin-semaphorin III/D-mediated chemorepulsive signals play a crucial role in peripheral nerve projection in mice. Neuron 19:995-1005.
Keleman, K., and Dickson, B.J. (2001). Short and long-range repulsion by the Drosophila Unc5 netrin receptor. Neuron 32:605-617.
Kolodziej, P. A., Timpe, L. C., Mitchell, K. J., Fried, S. R., Goodman, C. S., et al. (1996).
frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance. Cell 87:197-204.
Kruger, R.P., Lee, J., Li, W. and Guan, K.-L. (2004). Mapping netrin receptor binding reveals domains of Unc5 regulating its tyrosine phosphorylation. J. Neurosci.
24:10826-10834.
Lee, K. J., Mendelsohn, M. and Jessell, T. M. (1998). Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord. Genes Dev. 12:3394-3407.
Li, H.S., Chen, J.H., Wu, W., Fagaly, T., Zhou, L., et al. (1999). Vertebrate slit, a secreted ligand for the transmembrane protein roundabout, is a repellent for olfactory bulb axons. Cell 96:807-818.
Li, W., Lee, J., Vikis, H.G., Lee, S.-H., Liu, G., Aurandt, J., Shen, T.-L., Fearon, E.R., Guan, J.-L., Han, M., et al. (2004). Activation of FAKand Src are receptor-proximal events required for netrin signaling. Nat. Neurosci. 7:1213-1221.
Liu, Z., Patel, K., Schmidt, H., Andrews, W., Pini, A. and Sundaresan, V. (2004).
Extracellular Ig domains 1 and 2 of Robo are important for ligand (Slit) binding. Mol.
Cell Neurosci. 26:232-240.
Liu, G., Li, W., Wang, L., Kar, A., Guan, K-L., et al. (2009). DSCAM functions as a netrin receptor in commissural axon pathfinding. PNAS 106:2951-2956.
Long, H., Sabatier, C., Ma, L., Plump, A., Yuan, W., et al. (2004). Conserved roles for Slit and Robo proteins in midline commissural axon guidance. Neuron 42:213-223.
Ly, A., Nikolav, A., Suresh, G., Zheng, Y., Tessier-Lavigne M., and Stein E. (2008).
DSCAM is a netrin receptor that collaborates with DCC in mediating turning response to netrin-1. Cell 133:1241-1254.
Lyuksyutova, A. I., Lu, C. C., Milanesio, N., King, L. A., Guo, N., et al. (2003).
Anterior-posterior guidance of commissural axons by Wnt-frizzled signaling. Science 302:1984-1988.
64
Malnic, B., Hirono, J., Sato, T. and Buck, L.B. (1999). Combinatorial receptor codes for odors. Cell 96:713-723
Metin, C., Deleglise, D., Serafini, T., Kennedy, T.E., and Tessier- Lavigne, M. (1997). A role for netrin-1 in the guidance of cortical efferent’s. Development 124:5063-5074.
Ming, G.-L., Song, H.-J., Berninger, B., Holt, C.E., Tessier-Lavigne, M. and Poo, M.- M.
(1997). cAMP-dependent growth cone guidance by netrin-1. Neuron 19:1225-1235.
Mombaerts, P., Wang, F., Dulac, C., Chao, S.K., Nemes, A., et al. (1996). Visualizing an olfactory sensory map. Cell 87:675-686.
Monnier, P. P., Sierra, A., Macchi, P., Deitinghoff, L., Andersen, J. S., et al. (2002).
RGM is a repulsive guidance molecule for retinal axons. Nature 419:392-395.
Moore, S.W., Correia, J.P., Sun, K.L.W., Pool, M., Fournier, A.E., and Kennedy, T.E.
(2008). Rho inhibition recruits DCC to the neuronal plasma membrane and enhances axon chemoattraction to netrin 1. Development 135:2855-2864.
Murase, S. and Horwitz, A.F. (2002). Deleted in colorectal carcinoma and differentially expressed integrins mediatethe directional migration of neural precursors in the rostral migratory stream. J. Neurosci. 22:3568-79.
Muroyama, Y., Fujihara, M., Ikeya, M., Kondoh, H. and Takada, S. (2002). Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord. Genes Dev. 16:548-553.
Nagy, A., Gertsenstein, M., Vintersten, R., Behringer, R. Manipulating the Mouse Embryo: (2003). A Laboratory manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, ed. 3).
Nakayama, M., Nakajima, D., Nagase, T., Nomura, N., Seki, N. and Ohara, O. (1998).
Identification of high-molecular-weight proteins with multiple EGF-like motifs by motif-trap screening. Genomics 51:27-34.
Naser, I.B., Su, Y., Islam, S.M., Shinmyo, Y., Zhang, S., et al. (2009). Analysis of a repulsive axon guidance molecule, draxin, on ventrally directed axon projection in chick early embryonic midbrain. Dev. Biol. 332:351-359.
Nguyen-Ba-Charvet, K.T., Brose, K., Marillat, V., Kidd, T., Goodman, C.S., et al. (1999).
Slit 2 mediated chemorepulsion and collapse of developing forebrain axons. Neuron 22:463-473.
Nguyen-Ba-Charvet, K.T., Plump, A.S., Tessier-Lavigne, M. and Chedotal, A. (2002).
Slit1 and Slit2 proteins control the development of the lateral olfactory tract. J. Neurosci.
22:5473-5480.
Niederkofler, V., Salie, R., Sigrist, M. and Arber, S. (2004). Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J. Neurosci. 24:808-818.
Nishiyama, M., Hoshino, A., Tsai, L., Henley, J.R., Goshima, Y., et al. (2003). Cyclic AMP/GMP-dependent modulation of Ca2+channels sets the polarity of nerve growth-cone turning. Nature 423:990-995.
Ohta, K., Tannahill, D., Yoshida, K., Johnson, A. R., Cook, G. M. and Keynes, R. J.
(1999). Embryonic lens repel retinal ganglion cell axons. Dev. Biol. 211:124-132.
O`Leary, D.D. and Wilkinson, D.G. (1999). Eph receptors and ephrins in neural development. Curr. Opin. Neurobiol. 9:65-73.
Okada, A., Charron, F., Morin, S., Shin, D.S., Wong, K., et al. (2006). Boc is a receptor
66
Okafuji, T. and Tanaka, H. (2005). Expression pattern of LINGO-1 in the developing nervous system of the chick embryo. Gene Exp. Pattern 6:57-62.
Pasterkamp, R.J., Peschon, J.J., Spriggs, M.K., and Kolodkin, A.L. (2003). Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature 424:398-404.
Parra, L.M. and Zou, Y. (2009). Sonic hedgehog induces response of commissural axons to Semaphorin repulsion during midline crossing. Nat. Neurosci. 13:29-35.
Pini, A. (1993). Chemorepulsion of axons in the developing mammalian central nervous system. Science 261:95-98.
Poliakov, A., Cotrina, M.,and Wilkinson, D.G. (2004). Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly. Dev. Cell 7:465-480.
Rajagopalan, S., Deitinghoff, L., Davis, D., Conrad, S., Skutella, T., Chedota, A.,
Mueller, B. K., and Strittmatter, S. M. (2004). Neogenin mediates the action of repulsive guidance molecule. Nature Cell Biology 6, 756-762.
Raper, J.A. (2000). Semaphorins and their receptors in vertebrates and invertebrates.
Curr.Opin.Neurobiol. 10:88-94.
Rinaldi, A. (2007). The scent of life:the exquisite complexity of the sense of smell in animals and humans. EMBO Reports. 8:629-633.
Rothberg, J.M., Hartley, D.A., Walther, Z. and Artavanis-Tsakonas, S. (1988). Slit: an EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system. Cell 55:1047-1059.
Rothberg, J.M., Jacobs, J.R., Goodman, C.S. and Artavanis-Tsakonas, S. (1990). Slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains. Genes Dev. 4:2169-2187.
Sahay, A., Molliver, M.E., Ginty, D.D. and Kolodkin, A.L. (2003). Semaphorin 3F is critical for development of limbic system circuitry and is required in neurons for selective CNS axon guidance events. J. Neurosci. 23:6671-6680
Sabatier, C., Plump, A.S., Le, M., Brose, K., Tamada, A., et al. (2004). The divergent Robo family protein rig-1/Robo3 is a negative regulator of slit responsiveness required for midline crossing by commissural axons. Cell 117:157-169.
Sato, Y., Hirata, T., Ogawa, M. and Fujisawa, H. (1998). Requirement for early-generated neurons recognized by monoclonal antibody lot1 in the formation of lateral olfactory tract. J. Neurosci. 18:7800-7810.
Schwob, J.E. and Price, J.L. (1984). The development of axonal connections in the central olfactory system of rats. J. Comp. Neurol. 223:177-202.
Seeger, M., Tear, G., Ferres-Marco, D. and Goodman, C.S. (1993). Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron 10:409–26.
Serafini, T., Kennedy, T. E., Galko, M. J., Mirzayan, C., Jessell, T. M. and Tessier-Lavigne, M. (1994). The netrins define a family of axon outgrowth promoting proteins homologous to C. elegans UNC-6. Cell 78:409-424.
Shimamura, K. and Takeichi, M. (1992). Local and transient expression of E-cadherin involved in mouse embryonic brain morphogenesis. Development 116:1011-1019.
Shipley, M.T. and Ennis, M. (1996). Functional organization of olfactory system, J.
Neurobiol. 30:123-176.
Shu, T. and Richards, L. J. (2001). Cortical axon guidance by the glial wedge during the development of the corpus callosum. J. Neurosci. 21:2749-2758.
68
Song, H. J. and Poo, M. M. (1999). Signal transduction underlying growth cone guidance by diffusible factors. Curr. Opin. Neurobiol. 9:355-363.
Stein, E. and Tessier-Lavigne, M. (2001). Hierarchical organization of guidance receptors: silencing of netrin attraction by slit hrough a robo/DCC receptor complex.
Science 291: 1928-1938.
Sugisaki, N., Hirata, T., Naruse, I., Kawakami, A., Kitsukawa, T. and Fujisawa, H.
(1996). Positional cues that are strictly localized in the telencephalon induce preferential growth of mitral cells axons. J. Neurobiol. 29:127-137.
Taniguchi, M., Nagao. H., Takahashi, Y.K., Yamaguchi, M., Mitsui, S., Yagi, T., Mori, K., and Shimizu, T. (2003). Distorted odor maps in the olfactory bulb of semaphorin 3A-deficient mice. J Neurosci. 23:1390-1397.
Teleman, A. A., Strigini, M. and Cohen, S. M. (2001). Shaping morphogen gradients.
Cell 105:559 -562.
Tessier-Lavigne, M. and Goodman, C. S. (1996). The molecular biology of axon guidance. Science 274:1123-1133.
Tomioka, N., Osumi, N., Sato, Y., Inoue, T., Nakamura, S., et al. (2000). Neocortical origin and tangential migration of guidepost neurons in the lateral olfactory tract. J.
Neurosci. 20:5802 -5812.
Trousse, F., Marti, E., Gruss, P., Torres, M. and Bovolenta, P. (2001). Control of retinal ganglion cell axon growth: a new role for Sonic hedgehog. Development 128:3927 -3933.
Wang, H.U., Chen, Z.-F. and Anderson, D.J. (1998). Molecular distinction and
angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93:741-753.
Wang, K.H., Brose, K., Arnott, D., Kidd, T., Goodman, C.S., et al. (1999). Biochemical
purification of a mammalian Slit protein as a positive regulator of sensory axon elongation and branching. Cell 96:771-784.
Wen, Z. and Zheng, J.Q. (2006). Directional guidance of nerve growth cones. Curr. Opin.
Neurobiol. 16:52-58.
Winberg, M. L., Tamagnone, L., Bai, J., Comoglio, P.M., Montell, D. and Goodman, C.S.
(2001) The transmembrane protein off-track associates with plexins and functions downstream of semaphorin signaling during axon guidance. Neuron 32:53-62.
Wilkinson, D.G. (2001). Multiple roles of Eph receptors and ephrins in neural development. Nat. Rev. Neurosci. 2:155-164.
Wu, W., Wong, K., Chen, J., Jiang, Z.-H., Dupuis, S., Wu, J. and Rao, Y. (1999).
Directional guidance of neuronal migration in the olfactory system by the protein Slit.
Nature 400: 331-336.
Yee, K.T., Simon, H.H., Tessier-Lavigne, M., and O’Leary, D.M. (1999). Extension of long leading processes and neuronal migrtion in the mammalian brain directed by chemoattractant netrin-1. Neuron 24:607-622.
Yu, T.W. and Bargmann, C.I. (2001). Dynamic regulation of axon guidance. Nat.
Neurosci. 4:11769-1176.
Yu, T.W., Hao, J.C., Lim, W., Tessier-Lavigne, M. and Bargmann, C.I. (2002). Shared receptors in axon guidance: Sax-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function. Nature Neurosci. 5, 1147-1154.
Yuan, S.S., Cox, L.A., Dasika, G.K. and Lee, E.Y. (1999). Cloning and functional studies of a novel gene aberrantly expressed in RB-deficient embryos. Dev. Biol.
207:62–75.