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Biological Chemistry

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Volume 395, Issue 5

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In vivo functions of small GTPases in neocortical development

Bhavin Shah
  • Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, Schloßplatz 5, D-48149 Münster, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Andreas W. Püschel
  • Corresponding author
  • Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, Schloßplatz 5, D-48149 Münster, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2014-01-04 | DOI: https://doi.org/10.1515/hsz-2013-0277

Abstract

The complex mammalian cortex develops from a simple neuroepithelium through the proliferation of neuronal progenitors, their asymmetric division and cell migration. Newly generated neurons transiently assume a multipolar morphology before they polarize to form a trailing axon and a leading process that is required for their radial migration. The polarization and migration events during cortical development are under the control of multiple signaling cascades that coordinate the different cellular processes involved in neuronal differentiation. GTPases perform essential functions at different stages of neuronal development as central components of these pathways. They have been widely studied using cell lines and primary neuronal cultures but their physiological function in vivo still remains to be explored in many cases. Here we review the function of GTPases that have been studied genetically by the analysis of the embryonic nervous system in knockout mice. The phenotype of these mutants has highlighted the importance of GTPases for different steps of development by orchestrating cytoskeletal rearrangements and neuronal polarization.

Keywords: cortical development; knockout mouse; neuronal polarity; neuronal progenitor

References

  • Anthony, T.E., Klein, C., Fishell, G., and Heintz, N. (2004). Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron 41, 881–890.CrossrefGoogle Scholar

  • Ballif, B.A., Arnaud, L., and Cooper, J.A. (2003). Tyrosine phosphorylation of Disabled-1 is essential for Reelin-stimulated activation of Akt and Src family kinases. Brain Res. Mol. Brain Res. 117, 152–159.Google Scholar

  • Barnes, A.P. and Polleux, F. (2009). Establishment of axon-dendrite polarity in developing neurons. Annu. Rev. Neurosci. 32, 347–381.CrossrefGoogle Scholar

  • Barnes, A.P., Solecki, D., and Polleux, F. (2008). New insights into the molecular mechanisms specifying neuronal polarity in vivo. Curr. Opin. Neurobiol. 18, 44–52.CrossrefGoogle Scholar

  • Bielas, S., Higginbotham, H., Koizumi, H., Tanaka, T., and Gleeson, J.G. (2004). Cortical neuronal migration mutants suggest separate but intersecting pathways. Annu. Rev. Cell Dev. Biol. 20, 593–618.CrossrefGoogle Scholar

  • Bock, H.H. and Herz, J. (2003). Reelin activates SRC family tyrosine kinases in neurons. Curr. Biol. 13, 18–26.CrossrefGoogle Scholar

  • Bolis, A., Corbetta, S., Cioce, A., and de Curtis, I. (2003). Differential distribution of Rac1 and Rac3 GTPases in the developing mouse brain: implications for a role of Rac3 in Purkinje cell differentiation. Eur. J. Neurosci. 18, 2417–2424.Google Scholar

  • Breunig, J.J., Haydar, T.F., and Rakic, P. (2011). Neural stem cells: historical perspective and future prospects. Neuron 70, 614–625.CrossrefGoogle Scholar

  • Bultje, R.S., Castaneda-Castellanos, D.R., Jan, L.Y., Jan, Y.N., Kriegstein, A.R., and Shi, S.H. (2009). Mammalian Par3 regulates progenitor cell asymmetric division via notch signaling in the developing neocortex. Neuron 63, 189–202.CrossrefGoogle Scholar

  • Cappello, S., Attardo, A., Wu, X., Iwasato, T., Itohara, S., Wilsch-Bräuninger, M., Eilken, H., Rieger, M., Schroeder, T., Huttner, W., et al. (2006). The Rho-GTPase cdc42 regulates neural progenitor fate at the apical surface. Nat. Neurosci. 9, 1099–1107.CrossrefGoogle Scholar

  • Cappello, S., Bohringer, C.R., Bergami, M., Conzelmann, K.K., Ghanem, A., Tomassy, G.S., Arlotta, P., Mainardi, M., Allegra, M., Caleo, M., et al. (2012). A radial glia-specific role of RhoA in double cortex formation. Neuron 73, 911–924.CrossrefGoogle Scholar

  • Chen, L., Liao, G., Yang, L., Campbell, K., Nakafuku, M., Kuan, C.Y., and Zheng, Y. (2006). Cdc42 deficiency causes Sonic hedgehog-independent holoprosencephaly. Proc. Natl. Acad. Sci. USA 103, 16520–16525.CrossrefGoogle Scholar

  • Chen, L., Liao, G., Waclaw, R.R., Burns, K.A., Linquist, D., Campbell, K., Zheng, Y., and Kuan, C.Y. (2007). Rac1 controls the formation of midline commissures and the competency of tangential migration in ventral telencephalic neurons. J. Neurosci. 27, 3884–3893.CrossrefGoogle Scholar

  • Cloetta, D., Thomanetz, V., Baranek, C., Lustenberger, R.M., Lin, S., Oliveri, F., Atanasoski, S., and Ruegg, M.A. (2013). Inactivation of mTORC1 in the developing brain causes microcephaly and affects gliogenesis. J. Neurosci. 33, 7799–7810.CrossrefGoogle Scholar

  • Corbetta, S., Gualdoni, S., Albertinazzi, C., Paris, S., Croci, L., Consalez, G.G., and de Curtis, I. (2005). Generation and characterization of Rac3 knockout mice. Mol. Cell. Biol. 25, 5763–5776.CrossrefGoogle Scholar

  • Corbetta, S., Gualdoni, S., Ciceri, G., Monari, M., Zuccaro, E., Tybulewicz, V.L., and de Curtis, I. (2009). Essential role of Rac1 and Rac3 GTPases in neuronal development. FASEB J. 23, 1347–1357.Google Scholar

  • Costa, M., Wen, G., Lepier, A., Schroeder, T., and Götz, M. (2008). Par-complex proteins promote proliferative progenitor divisions in the developing mouse cerebral cortex. Development. 135, 11–22.CrossrefGoogle Scholar

  • Czuchra, A., Wu, X., Meyer, H., van Hengel, J., Schroeder, T., Geffers, R., Rottner, K., and Brakebusch, C. (2005). Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells. Mol. Biol. Cell. 16, 4473–4484.CrossrefGoogle Scholar

  • D’Adamo, P., Menegon, A., Lo Nigro, C., Grasso, M., Gulisano, M., Tamanini, F., Bienvenu, T., Gedeon, A., Oostra, B., Wu, S., et al. (1998). Mutations in GDI1 are responsible for X-linked non-specific mental retardation. Nat. Genet. 19, 134–139.CrossrefGoogle Scholar

  • Del Río, J., Martínez, A., Auladell, C., and Soriano, E. (2000). Developmental history of the subplate and developing white matter in the murine neocortex. Neuronal organization and relationship with the main afferent systems at embryonic and perinatal stages. Cereb. Cortex 10, 784–801.CrossrefGoogle Scholar

  • Dubois, N.C., Hofmann, D., Kaloulis, K., Bishop, J.M., and Trumpp, A. (2006). Nestin-Cre transgenic mouse line Nes-Cre1 mediates highly efficient Cre/loxP mediated recombination in the nervous system, kidney, and somite-derived tissues. Genesis 44, 355–360.CrossrefGoogle Scholar

  • Eagleson, K.L., Schlueter McFadyen-Ketchum, L.J., Ahrens, E.T., Mills, P.H., Does, M.D., Nickols, J., and Levitt, P. (2007). Disruption of Foxg1 expression by knock-in of cre recombinase: effects on the development of the mouse telencephalon. Neuroscience 148, 385–399.CrossrefGoogle Scholar

  • Esteban, L., Vicario-Abejón, C., Fernández-Salguero, P., Fernández-Medarde, A., Swaminathan, N., Yienger, K., Lopez, E., Malumbres, M., McKay, R., Ward, J., et al. (2001). Targeted genomic disruption of H-ras and N-ras, individually or in combination, reveals the dispensability of both loci for mouse growth and development. Mol. Cell. Biol. 21, 1444–1452.CrossrefGoogle Scholar

  • Facchinetti, V., Ouyang, W., Wei, H., Soto, N., Lazorchak, A., Gould, C., Lowry, C., Newton, A.C., Mao, Y., Miao, R.Q., et al. (2008). The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J. 27, 1932–1943.CrossrefGoogle Scholar

  • Foster, R., Hu, K., Lu, Y., Nolan, K., Thissen, J., and Settleman, J. (1996). Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation. Mol. Cell. Biol. 16, 2689–2699.CrossrefGoogle Scholar

  • Franco, S., Martinez-Garay, I., Gil-Sanz, C., Harkins-Perry, S., and Müller, U. (2011). Reelin regulates cadherin function via Dab1/Rap1 to control neuronal migration and lamination in the neocortex. Neuron 69, 482–497.CrossrefGoogle Scholar

  • Frotscher, M. (2010). Role for Reelin in stabilizing cortical architecture. Trends Neurosci. 33, 407–414.CrossrefGoogle Scholar

  • Fukata, M., Nakagawa, M., and Kaibuchi, K. (2003). Roles of Rho-family GTPases in cell polarisation and directional migration. Curr. Opin. Cell Biol. 15, 590–597.CrossrefGoogle Scholar

  • Gao, P., Sultan, K.T., Zhang, X.J., and Shi, S.H. (2013). Lineage-dependent circuit assembly in the neocortex. Development 140, 2645–2655.CrossrefGoogle Scholar

  • Garvalov, B., Flynn, K., Neukirchen, D., Meyn, L., Teusch, N., Wu, X., Brakebusch, C., Bamburg, J., and Bradke, F. (2007). Cdc42 regulates cofilin during the establishment of neuronal polarity. J Neurosci. 27, 13117–13129.CrossrefGoogle Scholar

  • Goebbels, S., Bormuth, I., Bode, U., Hermanson, O., Schwab, M., and Nave, K.-A. (2006). Genetic targeting of principal neurons in neocortex and hippocampus of NEX-Cre mice. Genesis 44, 611–621.CrossrefGoogle Scholar

  • Govek, E.E., Newey, S.E., and Van Aelst, L. (2005). The role of the Rho GTPases in neuronal development. Genes Dev. 19, 1–49.CrossrefGoogle Scholar

  • Guo, H., Hong, S., Jin, X., Chen, R., Avasthi, P., Tu, Y., Ivanco, T., and Li, Y. (2000). Specificity and efficiency of Cre-mediated recombination in Emx1-Cre knock-in mice. Biochem. Biophys. Res. Commun. 273, 661–665.CrossrefGoogle Scholar

  • Gupta, A., Tsai, L.H., and Wynshaw-Boris, A. (2002). Life is a journey: a genetic look at neocortical development. Nat. Rev. Genet. 3, 342–355.CrossrefGoogle Scholar

  • Hall, A. and Lalli, G. (2010). Rho and Ras GTPases in axon growth, guidance, and branching. Cold Spring Harb. Perspect. Biol. 2, a001818.Google Scholar

  • Hartfuss, E., Galli, R., Heins, N., and Gotz, M. (2001). Characterization of CNS precursor subtypes and radial glia. Dev. Biol. 229, 15–30.Google Scholar

  • Hatanaka, Y. and Yamauchi, K. (2013). Excitatory cortical neurons with multipolar shape establish neuronal polarity by forming a tangentially oriented axon in the intermediate zone. Cereb. Cortex 23, 105–113.CrossrefGoogle Scholar

  • Heasman, S.J. and Ridley, A.J. (2008). Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat. Rev. Mol. Cell. Biol. 9, 690–701.CrossrefGoogle Scholar

  • Hebert, J.M. and McConnell, S.K. (2000). Targeting of cre to the Foxg1 (BF-1) locus mediates loxP recombination in the telencephalon and other developing head structures. Dev. Biol. 222, 296–306.CrossrefGoogle Scholar

  • Herz, J. and Chen, Y. (2006). Reelin, lipoprotein receptors and synaptic plasticity. Nat. Rev. Neurosci. 7, 850–859.CrossrefGoogle Scholar

  • Higginbotham, H., Guo, J., Yokota, Y., Umberger, N.L., Su, C.Y., Li, J., Verma, N., Hirt, J., Ghukasyan, V., Caspary, T., et al. (2013). Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation. Nat Neurosci. 16, 1000–1007.CrossrefGoogle Scholar

  • Iden, S. and Collard, J. (2008). Crosstalk between small GTPases and polarity proteins in cell polarization. Nat Rev Mol. Cell. Biol. 9, 846–859.CrossrefGoogle Scholar

  • Imai, F. (2006). Inactivation of aPKC results in the loss of adherens junctions in neuroepithelial cells without affecting neurogenesis in mouse neocortex. Development 133, 1735–44.Google Scholar

  • Jossin, Y. and Cooper, J. (2011). Reelin, Rap1 and N-cadherin orient the migration of multipolar neurons in the developing neocortex. Nat. Neurosci. 14, 697–703.CrossrefGoogle Scholar

  • Kahn, R.A., Cherfils, J., Elias, M., Lovering, R.C., Munro, S., and Schurmann, A. (2006). Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins. J. Cell Biol. 172, 645–650.CrossrefGoogle Scholar

  • Kassai, H., Terashima, T., Fukaya, M., Nakao, K., Sakahara, M., Watanabe, M., and Aiba, A. (2008). Rac1 in cortical projection neurons is selectively required for midline crossing of commissural axonal formation. Eur. J. Neurosci. 28, 257–267.CrossrefGoogle Scholar

  • Katayama, K., Melendez, J., Baumann, J.M., Leslie, J.R., Chauhan, B.K., Nemkul, N., Lang, R.A., Kuan, C.Y., Zheng, Y., and Yoshida, Y. (2011). Loss of RhoA in neural progenitor cells causes the disruption of adherens junctions and hyperproliferation. Proc. Natl. Acad. Sci. USA 108, 7607–7612.CrossrefGoogle Scholar

  • Kawauchi, T., Sekine, K., Shikanai, M., Chihama, K., Tomita, K., Kubo, K.-I., Nakajima, K., Nabeshima, Y.-I., and Hoshino, M. (2010). Rab GTPases-dependent endocytic pathways regulate neuronal migration and maturation through N-cadherin trafficking. Neuron 67, 588–602.CrossrefGoogle Scholar

  • Kowalczyk, T., Pontious, A., Englund, C., Daza, R.A., Bedogni, F., Hodge, R., Attardo, A., Bell, C., Huttner, W.B., and Hevner, R.F. (2009). Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex. Cereb. Cortex 19, 2439–2450.CrossrefGoogle Scholar

  • Kuo, G., Arnaud, L., Kronstad-O’Brien, P., and Cooper, J.A. (2005). Absence of Fyn and Src causes a reeler-like phenotype. J. Neurosci. 25, 8578–8586.CrossrefGoogle Scholar

  • Laplante, M. and Sabatini, D.M. (2012). mTOR signaling in growth control and disease. Cell 149, 274–293.CrossrefGoogle Scholar

  • Leone, D.P., Srinivasan, K., Brakebusch, C., and McConnell, S.K. (2010). The rho GTPase Rac1 is required for proliferation and survival of progenitors in the developing forebrain. Dev. Neurobiol. 70, 659–678.Google Scholar

  • Lewis, T.L., Jr., Courchet, J., and Polleux, F. (2013). Cell biology in neuroscience: Cellular and molecular mechanisms underlying axon formation, growth, and branching. J. Cell Biol. 202, 837–848.Google Scholar

  • Li, Y.H., Ghavampur, S., Bondallaz, P., Will, L., Grenningloh, G., and Püschel, A.W. (2009). Rnd1 regulates axon extension by enhancing the microtubule destabilizing activity of SCG10. J. Biol. Chem. 284, 363–371.Google Scholar

  • Liang, H., Hippenmeyer, S., and Ghashghaei, H.T. (2012). A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors. Biol. Open. 1, 1200–1203.CrossrefGoogle Scholar

  • LoTurco, J.J. and Bai, J. (2006). The multipolar stage and disruptions in neuronal migration. Trends Neurosci. 29, 407–413.CrossrefGoogle Scholar

  • Marthiens, V. and ffrench-Constant, C. (2009). Adherens junction domains are split by asymmetric division of embryonic neural stem cells. EMBO Rep. 10, 515–520.CrossrefGoogle Scholar

  • Meyer, G. (2010). Building a human cortex: the evolutionary differentiation of Cajal-Retzius cells and the cortical hem. J. Anat. 217, 334–343.Google Scholar

  • Mocholi, E., Ballester-Lurbe, B., Arque, G., Poch, E., Peris, B., Guerri, C., Dierssen, M., Guasch, R.M., Terrado, J., and Perez-Roger, I. (2011). RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice. PLoS One 6, e19236.Google Scholar

  • Nadarajah, B. and Parnavelas, J.G. (2002). Modes of neuronal migration in the developing cerebral cortex. Nat. Rev. Neurosci. 3, 423–432.CrossrefGoogle Scholar

  • Nadarajah, B., Brunstrom, J., Grutzendler, J., Wong, R., and Pearlman, A. (2001). Two modes of radial migration in early development of the cerebral cortex. Nat. Neurosci. 4, 143–150.CrossrefGoogle Scholar

  • Nguyen, L., Besson, A., Heng, J.I., Schuurmans, C., Teboul, L., Parras, C., Philpott, A., Roberts, J.M., and Guillemot, F. (2006). p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex. Genes Dev. 20, 1511–1524.CrossrefGoogle Scholar

  • Noctor, S., Martínez-Cerdeño, V., Ivic, L., and Kriegstein, A. (2004). Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci. 7, 136–144.CrossrefGoogle Scholar

  • Ogawa, M., Miyata, T., Nakajima, K., Yagyu, K., Seike, M., Ikenaka, K., Yamamoto, H., and Mikoshiba, K. (1995). The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons. Neuron 14, 899–912.CrossrefGoogle Scholar

  • Oinuma, I., Katoh, H., and Negishi, M. (2007). R-Ras controls axon specification upstream of glycogen synthase kinase-3beta through integrin-linked kinase. J. Biol. Chem. 282, 303–318.Google Scholar

  • Pacary, E., Heng, J., Azzarelli, R., Riou, P., Castro, D., Lebel-Potter, M., Parras, C., Bell, D.M., Ridley, A.J., Parsons, M., et al. (2011). Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling. Neuron 69, 1069–1084.CrossrefGoogle Scholar

  • Pacary, E., Azzarelli, R., and Guillemot, F. (2013). Rnd3 coordinates early steps of cortical neurogenesis through actin-dependent and -independent mechanisms. Nat. Commun. 4, 1635.Google Scholar

  • Park, T.J. and Curran, T. (2008). Crk and Crk-like play essential overlapping roles downstream of disabled-1 in the Reelin pathway. J Neurosci. 28, 13551–13562.CrossrefGoogle Scholar

  • Peng, X., Lin, Q., Liu, Y., Jin, Y., Druso, J.E., Antonyak, M.A., Guan, J.L., and Cerione, R.A. (2013). Inactivation of Cdc42 in embryonic brain results in hydrocephalus with ependymal cell defects in mice. Protein Cell. 4, 231–242.Google Scholar

  • Peris, B., Gonzalez-Granero, S., Ballester-Lurbe, B., Garcia-Verdugo, J.M., Perez-Roger, I., Guerri, C., Terrado, J., and Guasch, R.M. (2012). Neuronal polarization is impaired in mice lacking RhoE expression. J. Neurochem. 121, 903–914.CrossrefGoogle Scholar

  • Pfeffer, S. (2001). Rab GTPases: specifying and deciphering organelle identity and function. Trends Cell. Biol. 11, 487–491.CrossrefGoogle Scholar

  • Pinto, L., Mader, M.T., Irmler, M., Gentilini, M., Santoni, F., Drechsel, D., Blum, R., Stahl, R., Bulfone, A., Malatesta, P., et al. (2008). Prospective isolation of functionally distinct radial glial subtypes – lineage and transcriptome analysis. Mol. Cell. Neurosci. 38, 15–42.CrossrefGoogle Scholar

  • Riento, K., Guasch, R., Garg, R., Jin, B., and Ridley, A. (2003). RhoE binds to ROCK I and inhibits downstream signaling. Mol. Cell. Biol. 23, 4219–4229.CrossrefGoogle Scholar

  • Sakakibara, A., Sato, T., Ando, R., Noguchi, N., Masaoka, M., and Miyata, T. (2013). Dynamics of centrosome translocation and microtubule organization in neocortical neurons during distinct modes of polarization. Cereb. Cortex, in press.Google Scholar

  • Schluter, O.M., Schmitz, F., Jahn, R., Rosenmund, C., and Sudhof, T.C. (2004). A complete genetic analysis of neuronal Rab3 function. J. Neurosci. 24, 6629–6637.CrossrefGoogle Scholar

  • Schmid, R. and Anton, E. (2003). Role of integrins in the development of the cerebral cortex. Cereb. Cortex 13, 219–224.CrossrefGoogle Scholar

  • Schwamborn, J. and Püschel, A. (2004). The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity. Nat. Neurosci. 7, 923–929.CrossrefGoogle Scholar

  • Tabata, H. and Nakajima, K. (2003). Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex. J. Neurosci. 23, 9996–10001.Google Scholar

  • Tahirovic, S., Hellal, F., Neukirchen, D., Hindges, R., Garvalov, B.K., Flynn, K.C., Stradal, T.E., Chrostek-Grashoff, A., Brakebusch, C., and Bradke, F. (2010). Rac1 regulates neuronal polarization through the WAVE complex. J. Neurosci. 30, 6930–6943.CrossrefGoogle Scholar

  • Talens-Visconti, R., Peris, B., Guerri, C., and Guasch, R.M. (2010). RhoE stimulates neurite-like outgrowth in PC12 cells through inhibition of the RhoA/ROCK-I signalling. J. Neurochem. 112, 1074–1087.CrossrefGoogle Scholar

  • Thomanetz, V., Angliker, N., Cloetta, D., Lustenberger, R.M., Schweighauser, M., Oliveri, F., Suzuki, N., and Ruegg, M.A. (2013). Ablation of the mTORC2 component rictor in brain or Purkinje cells affects size and neuron morphology. J. Cell Biol. 201, 293–308.CrossrefGoogle Scholar

  • Thoreen, C.C., Chantranupong, L., Keys, H.R., Wang, T., Gray, N.S., and Sabatini, D.M. (2012). A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 485, 109–113.Google Scholar

  • Tissir, F. and Goffinet, A.M. (2003). Reelin and brain development. Nat. Rev. Neurosci. 4, 496–505.CrossrefGoogle Scholar

  • Trommsdorff, M., Gotthardt, M., Hiesberger, T., Shelton, J., Stockinger, W., Nimpf, J., Hammer, R., Richardson, J., and Herz, J. (1999). Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. Cell 97, 689–701.CrossrefGoogle Scholar

  • Wennerberg, K., Rossman, K.L., and Der, C.J. (2005). The Ras superfamily at a glance. J. Cell Sci. 118, 843–846.CrossrefGoogle Scholar

  • Wu, S.X., Goebbels, S., Nakamura, K., Nakamura, K., Kometani, K., Minato, N., Kaneko, T., Nave, K.A., and Tamamaki, N. (2005). Pyramidal neurons of upper cortical layers generated by NEX-positive progenitor cells in the subventricular zone. Proc. Natl. Acad. Sci. USA 102, 17172–17177.CrossrefGoogle Scholar

  • Wullschleger, S., Loewith, R., and Hall, M.N. (2006). TOR signaling in growth and metabolism. Cell 124, 471–484.CrossrefGoogle Scholar

  • Xi Lin, B.L., Xiangsheng Yang, Xiaojing Yue, Lixia Diao, Jing Wang, and Jiang Chang (2013). Genetic deletion of Rnd3 results in aqueductal stenosis leading to hydrocephalus through up-regulation of Notch signaling. Proc. Natl. Acad. Sci. USA 110, 8236–8241.CrossrefGoogle Scholar

  • Yoshida, M., Assimacopoulos, S., Jones, K.R., and Grove, E.A. (2006). Massive loss of Cajal-Retzius cells does not disrupt neocortical layer order. Development 133, 537–545.Google Scholar

  • Yoshimura, T., Arimura, N., and Kaibuchi, K. (2006a). Signaling networks in neuronal polarization. J. Neurosci. 26, 10626–10630.CrossrefGoogle Scholar

  • Yoshimura, T., Arimura, N., Kawano, Y., Kawabata, S., Wang, S., and Kaibuchi, K. (2006b). Ras regulates neuronal polarity via the PI3-kinase/Akt/GSK-3β/CRMP-2 pathway. Biochem. Biophys. Res. Commun. 340, 62–68.Google Scholar

  • Zhang, Q., Hu, J., and Ling, K. (2013). Molecular views of Arf-like small GTPases in cilia and ciliopathies. Exp. Cell Res. 319, 2316–2322.CrossrefGoogle Scholar

  • Zou, J., Zhou, L., Du, X.X., Ji, Y., Xu, J., Tian, J., Jiang, W., Zou, Y., Yu, S., Gan, L., et al. (2011). Rheb1 is required for mTORC1 and myelination in postnatal brain development. Dev. Cell. 20, 97–108.CrossrefGoogle Scholar

  • Zovein, A.C., Luque, A., Turlo, K.A., Hofmann, J.J., Yee, K.M., Becker, M.S., Fassler, R., Mellman, I., Lane, T.F., and Iruela-Arispe, M.L. (2010). Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a Par3-dependent mechanism. Dev Cell. 18, 39–51.CrossrefGoogle Scholar

About the article

Bhavin Shah

Bhavin Shah studied Biology at the Universities of Mumbai and Pune (India). He is currently doing his PhD at the University of Münster. His PhD project deals with the role of Rap1 GTPases and their upstream regulators in neuronal polarity and cortical development.

Andreas W. Püschel

Andreas Püschel studied Biology at the Universities of Bonn and Heidelberg. During his PhD he worked from 1986 to 1989 with Peter Gruss first at the ZMBH in Heidelberg and then at the Max Planck Institute for Biophysical Chemistry in Göttingen on the regulation of Hox genes. After postdoctoral studies on Pax genes in zebrafish at the Institute of Neuroscience in Eugene (Oregon), he joined the Max Planck Institute for Brain Research in Frankfurt in 1992, where he investigated the role of semaphorins as axon guidance molecules. In 2001, he was appointed Professor in Molecular Biology at the Institute for Molecular Cell Biology at the University of Münster. His current research focuses on identifying and analyzing the signals that direct the differentiation of neurons using knockout mice and live cell imaging.


Corresponding author: Andreas W. Püschel, Institut für Molekulare Zellbiologie, Westfälische Wilhelms-Universität, Schloßplatz 5, D-48149 Münster, Germany, e-mail:


Received: 2013-11-19

Accepted: 2013-12-24

Published Online: 2014-01-04

Published in Print: 2014-05-01


Citation Information: Biological Chemistry, Volume 395, Issue 5, Pages 465–476, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2013-0277.

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[1]
Alejandro López Tobón, Megalakshmi Suresh, Jing Jin, Alessandro Vitriolo, Thorben Pietralla, Kerry Tedford, Michael Bossenz, Kristina Mahnken, Friedemann Kiefer, Giuseppe Testa, Klaus-Dieter Fischer, and Andreas W. Püschel
Scientific Reports, 2018, Volume 8, Number 1
[2]
Catherine H H Hor and Eyleen L K Goh
Cerebral Cortex, 2018
[4]
Roberta Azzarelli, François Guillemot, and Emilie Pacary
Frontiers in Neuroscience, 2015, Volume 9

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