Signal Transduction/physiology; GDNF; GFRα1; cortical precursors; neuronal differentiation; postmitotic neurons
Abstract :
[en] The balance between factors leading to proliferation and differentiation of cortical neural precursors (CNPs) determines the correct cortical development. In this work, we show that GDNF and its receptor GFRα1 are expressed in the neocortex during the period of cortical neurogenesis. We show that the GDNF/GFRα1 complex inhibits the self-renewal capacity of mouse CNP cells induced by fibroblast growth factor 2 (FGF2), promoting neuronal differentiation. While GDNF leads to decreased proliferation of cultured cortical precursor cells, ablation of GFRα1 in glutamatergic cortical precursors enhances its proliferation. We show that GDNF treatment of CNPs promoted morphological differentiation even in the presence of the self-renewal-promoting factor, FGF2. Analysis of GFRα1-deficient mice shows an increase in the number of cycling cells during cortical development and a reduction in dendrite development of cortical GFRα1-expressing neurons. Together, these results indicate that GDNF/GFRα1 signaling plays an essential role in regulating the proliferative condition and the differentiation of cortical progenitors.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bonafina, Antonela ; Université de Liège - ULiège > Stem Cells-Molecular Regulation of Neurogenesis
Fontanet, Paula Aldana
Paratcha, Gustavo
Ledda, Fernanda
Language :
English
Title :
GDNF/GFRα1 Complex Abrogates Self-Renewing Activity of Cortical Neural Precursors Inducing Their Differentiation.
Anderson, S.A., Eisenstat, D.D., Shi, L., Rubenstein, J.L., Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278 (1997), 474–476.
Anderson, S.A., Kaznowski, C.E., Horn, C., Rubenstein, J.L., McConnell, S.K., Distinct origins of neocortical projection neurons and interneurons in vivo. Cereb. Cortex 12 (2002), 702–709.
Andreu, Z., Khan, M.A., Gonzalez-Gomez, P., Negueruela, S., Hortiguela, R., San Emeterio, J., Ferron, S.R., Martinez, G., Vidal, A., Farinas, I., et al. The cyclin-dependent kinase inhibitor p27 kip1 regulates radial stem cell quiescence and neurogenesis in the adult hippocampus. Stem Cells 33 (2015), 219–229.
Antonopoulos, J., Pappas, I.S., Parnavelas, J.G., Activation of the GABAA receptor inhibits the proliferative effects of bFGF in cortical progenitor cells. Eur. J. Neurosci. 9 (1997), 291–298.
Arvidsson, A., Kokaia, Z., Airaksinen, M.S., Saarma, M., Lindvall, O., Stroke induces widespread changes of gene expression for glial cell line-derived neurotrophic factor family receptors in the adult rat brain. Neuroscience 106 (2001), 27–41.
Barnabe-Heider, F., Miller, F.D., Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways. J. Neurosci. 23 (2003), 5149–5160.
Bartkowska, K., Paquin, A., Gauthier, A.S., Kaplan, D.R., Miller, F.D., Trk signaling regulates neural precursor cell proliferation and differentiation during cortical development. Development 134 (2007), 4369–4380.
Bespalov, M.M., Sidorova, Y.A., Tumova, S., Ahonen-Bishopp, A., Magalhaes, A.C., Kulesskiy, E., Paveliev, M., Rivera, C., Rauvala, H., Saarma, M., Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin. J. Cell Biol. 192 (2011), 153–169.
Borello, U., Cobos, I., Long, J.E., McWhirter, J.R., Murre, C., Rubenstein, J.L., FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development. Neural Dev., 3, 2008, 17.
Burazin, T.C., Gundlach, A.L., Localization of GDNF/neurturin receptor (c-ret, GFRalpha-1 and alpha-2) mRNAs in postnatal rat brain: differential regional and temporal expression in hippocampus, cortex and cerebellum. Brain Res. Mol. Brain Res. 73 (1999), 151–171.
Burdon, T., Smith, A., Savatier, P., Signalling, cell cycle and pluripotency in embryonic stem cells. Trends Cell Biol. 12 (2002), 432–438.
Bystron, I., Blakemore, C., Rakic, P., Development of the human cerebral cortex: Boulder Committee revisited. Nat. Rev. Neurosci. 9 (2008), 110–122.
Canty, A.J., Dietze, J., Harvey, M., Enomoto, H., Milbrandt, J., Ibanez, C.F., Regionalized loss of parvalbumin interneurons in the cerebral cortex of mice with deficits in GFRalpha1 signaling. J. Neurosci. 29 (2009), 10695–10705.
Chambers, C.B., Peng, Y., Nguyen, H., Gaiano, N., Fishell, G., Nye, J.S., Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors. Development 128 (2001), 689–702.
Charoy, C., Nawabi, H., Reynaud, F., Derrington, E., Bozon, M., Wright, K., Falk, J., Helmbacher, F., Kindbeiter, K., Castellani, V., Gdnf activates midline repulsion by Semaphorin3B via NCAM during commissural axon guidance. Neuron 75 (2012), 1051–1066.
Cholfin, J.A., Rubenstein, J.L., Patterning of frontal cortex subdivisions by Fgf17. Proc. Natl. Acad. Sci. USA 104 (2007), 7652–7657.
Christensen, C., Lauridsen, J.B., Berezin, V., Bock, E., Kiselyov, V.V., The neural cell adhesion molecule binds to fibroblast growth factor receptor 2. FEBS Lett. 580 (2006), 3386–3390.
Ford-Perriss, M., Abud, H., Murphy, M., Fibroblast growth factors in the developing central nervous system. Clin. Exp. Pharmacol. Physiol. 28 (2001), 493–503.
Francavilla, C., Cattaneo, P., Berezin, V., Bock, E., Ami, D., de Marco, A., Christofori, G., Cavallaro, U., The binding of NCAM to FGFR1 induces a specific cellular response mediated by receptor trafficking. J. Cell Biol. 187 (2009), 1101–1116.
Francavilla, C., Loeffler, S., Piccini, D., Kren, A., Christofori, G., Cavallaro, U., Neural cell adhesion molecule regulates the cellular response to fibroblast growth factor. J. Cell Sci. 120 (2007), 4388–4394.
Fukuchi-Shimogori, T., Grove, E.A., Neocortex patterning by the secreted signaling molecule FGF8. Science 294 (2001), 1071–1074.
Garel, S., Huffman, K.J., Rubenstein, J.L., Molecular regionalization of the neocortex is disrupted in Fgf8 hypomorphic mutants. Development 130 (2003), 1903–1914.
Glazner, G.W., Mu, X., Springer, J.E., Localization of glial cell line-derived neurotrophic factor receptor alpha and c-ret mRNA in rat central nervous system. J. Comp. Neurol. 391 (1998), 42–49.
Golden, J.P., DeMaro, J.A., Osborne, P.A., Milbrandt, J., Johnson, E.M. Jr., Expression of neurturin, GDNF, and GDNF family-receptor mRNA in the developing and mature mouse. Exp. Neurol. 158 (1999), 504–528.
Gorski, J.A., Talley, T., Qiu, M., Puelles, L., Rubenstein, J.L., Jones, K.R., Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J. Neurosci. 22 (2002), 6309–6314.
Gotz, M., Stoykova, A., Gruss, P., Pax6 controls radial glia differentiation in the cerebral cortex. Neuron 21 (1998), 1031–1044.
Hansen, S.M., Kohler, L.B., Li, S., Kiselyov, V., Christensen, C., Owczarek, S., Bock, E., Berezin, V., NCAM-derived peptides function as agonists for the fibroblast growth factor receptor. J. Neurochem. 106 (2008), 2030–2041.
Haydar, T.F., Wang, F., Schwartz, M.L., Rakic, P., Differential modulation of proliferation in the neocortical ventricular and subventricular zones. J. Neurosci. 20 (2000), 5764–5774.
Hebert, J.M., Fishell, G., The genetics of early telencephalon patterning: some assembly required. Nat. Rev. Neurosci. 9 (2008), 678–685.
Irala, D., Bonafina, A., Fontanet, P.A., Alsina, F.C., Paratcha, G., Ledda, F., The GDNF-GFRalpha1 complex promotes the development of hippocampal dendritic arbors and spines via NCAM. Development 143 (2016), 4224–4235.
Iwasato, T., Datwani, A., Wolf, A.M., Nishiyama, H., Taguchi, Y., Tonegawa, S., Knopfel, T., Erzurumlu, R.S., Itohara, S., Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex. Nature 406 (2000), 726–731.
Jin, L., Hu, X., Feng, L., NT3 inhibits FGF2-induced neural progenitor cell proliferation via the PI3K/GSK3 pathway. J. Neurochem. 93 (2005), 1251–1261.
Kang, W., Wong, L.C., Shi, S.H., Hebert, J.M., The transition from radial glial to intermediate progenitor cell is inhibited by FGF signaling during corticogenesis. J. Neurosci. 29 (2009), 14571–14580.
Kiselyov, V.V., Skladchikova, G., Hinsby, A.M., Jensen, P.H., Kulahin, N., Soroka, V., Pedersen, N., Tsetlin, V., Poulsen, F.M., Berezin, V., et al. Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP. Structure 11 (2003), 691–701.
Konishi, Y., Yang, L.B., He, P., Lindhol, K., Lu, B., Li, R., Shen, Y., Deficiency of GDNF receptor GFRα1 in Alzheimer's neurons results in neuronal death. J. Neurosci. 34 (2014), 13127–13138.
Kowalczyk, T., Pontious, A., Englund, C., Daza, R.A., Bedogni, F., Hodge, R., Attardo, A., Bell, C., Huttner, W.B., Hevner, R.F., Intermediate neuronal progenitors (basal progenitors) produce pyramidal-projection neurons for all layers of cerebral cortex. Cereb. Cortex 19 (2009), 2439–2450.
Lenhard, T., Suter-Crazzolara, C., Developmental expression of GDNF, neurturin and their receptors in rat hippocampus. Neuroreport 9 (1998), 2927–2931.
Li, M., Price, D., Smith, A., Lineage selection and isolation of neural precursors from embryonic stem cells. Symp. Soc. Exp. Biol., 2001, 29–42.
LoTurco, J.J., Owens, D.F., Heath, M.J., Davis, M.B., Kriegstein, A.R., GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis. Neuron 15 (1995), 1287–1298.
Ma, W., Maric, D., Li, B.S., Hu, Q., Andreadis, J.D., Grant, G.M., Liu, Q.Y., Shaffer, K.M., Chang, Y.H., Zhang, L., et al. Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation. Eur. J. Neurosci. 12 (2000), 1227–1240.
Maric, D., Fiorio Pla, A., Chang, Y.H., Barker, J.L., Self-renewing and differentiating properties of cortical neural stem cells are selectively regulated by basic fibroblast growth factor (FGF) signaling via specific FGF receptors. J. Neurosci. 27 (2007), 1836–1852.
Meng, X., Lindahl, M., Hyvonen, M.E., Parvinen, M., de Rooij, D.G., Hess, M.W., Raatikainen-Ahokas, A., Sainio, K., Rauvala, H., Lakso, M., et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 287 (2000), 1489–1493.
Mira, H., Andreu, Z., Suh, H., Lie, D.C., Jessberger, S., Consiglio, A., San Emeterio, J., Hortiguela, R., Marques-Torrejon, M.A., Nakashima, K., et al. Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus. Cell Stem Cell 7 (2010), 78–89.
Molyneaux, B.J., Arlotta, P., Macklis, J.D., Molecular development of corticospinal motor neuron circuitry. Novartis Found. Symp. 288 (2007), 3–15 discussion 15-20, 96-18.
Ohkubo, Y., Uchida, A.O., Shin, D., Partanen, J., Vaccarino, F.M., Fibroblast growth factor receptor 1 is required for the proliferation of hippocampal progenitor cells and for hippocampal growth in mouse. J. Neurosci. 24 (2004), 6057–6069.
Paratcha, G., Ibanez, C.F., Ledda, F., GDNF is a chemoattractant factor for neuronal precursor cells in the rostral migratory stream. Mol. Cell Neurosci. 31 (2006), 505–514.
Paratcha, G., Ledda, F., Ibanez, C.F., The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 113 (2003), 867–879.
Pozas, E., Ibanez, C.F., GDNF and GFRalpha1 promote differentiation and tangential migration of cortical GABAergic neurons. Neuron 45 (2005), 701–713.
Qian, X., Davis, A.A., Goderie, S.K., Temple, S., FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells. Neuron 18 (1997), 81–93.
Raballo, R., Rhee, J., Lyn-Cook, R., Leckman, J.F., Schwartz, M.L., Vaccarino, F.M., Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J. Neurosci. 20 (2000), 5012–5023.
Rakic, P., A century of progress in corticoneurogenesis: from silver impregnation to genetic engineering. Cereb. Cortex 16:Suppl 1 (2006), i3–17.
Rash, B.G., Lim, H.D., Breunig, J.J., Vaccarino, F.M., FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis. J. Neurosci. 31 (2011), 15604–15617.
Saarma, M., GDNF - a stranger in the TGF-beta superfamily?. Eur. J. Biochem. 267 (2000), 6968–6971.
Shen, Q., Zhong, W., Jan, Y.N., Temple, S., Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. Development 129 (2002), 4843–4853.
Sholl, D.A., Dendritic organization in the neurons of the visual and motor cortices of the cat. J. Anat. 87 (1953), 387–406.
Stevens, H.E., Smith, K.M., Maragnoli, M.E., Fagel, D., Borok, E., Shanabrough, M., Horvath, T.L., Vaccarino, F.M., Fgfr2 is required for the development of the medial prefrontal cortex and its connections with limbic circuits. J. Neurosci. 30 (2010), 5590–5602.
Takashima, S., Kanatsu-Shinohara, M., Tanaka, T., Morimoto, H., Inoue, K., Ogonuki, N., Jijiwa, M., Takahashi, M., Ogura, A., Shinohara, T., Functional differences between GDNF-dependent and FGF2-dependent mouse spermatogonial stem cell self-renewal. Stem Cell Reports 4 (2015), 489–502.
Trupp, M., Scott, R., Whittemore, S.R., Ibanez, C.F., Ret-dependent and -independent mechanisms of glial cell line-derived neurotrophic factor signaling in neuronal cells. J. Biol. Chem. 274 (1999), 20885–20894.
Uesaka, T., Jain, S., Yonemura, S., Uchiyama, Y., Milbrandt, J., Enomoto, H., Conditional ablation of GFRalpha1 in postmigratory enteric neurons triggers unconventional neuronal death in the colon and causes a Hirschsprung's disease phenotype. Development 134 (2007), 2171–2181.
Vaccarino, F.M., Schwartz, M.L., Raballo, R., Nilsen, J., Rhee, J., Zhou, M., Doetschman, T., Coffin, J.D., Wyland, J.J., Hung, Y.T., Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis. Nat. Neurosci., 2, 1999, 848.
Vaccarino, F.M., Schwartz, M.L., Raballo, R., Rhee, J., Lyn-Cook, R., Fibroblast growth factor signaling regulates growth and morphogenesis at multiple steps during brain development. Curr. Top. Dev. Biol. 46 (1999), 179–200.
Weise, B., Janet, T., Grothe, C., Localization of bFGF and FGF-receptor in the developing nervous system of the embryonic and newborn rat. J. Neurosci. Res. 34 (1993), 442–453.
Weisstaub, N.V., Zhou, M., Lira, A., Lambe, E., Gonzalez-Maeso, J., Hornung, J.P., Sibille, E., Underwood, M., Itohara, S., Dauer, W.T., et al. Cortical 5-HT2A receptor signaling modulates anxiety-like behaviors in mice. Science 313 (2006), 536–540.
Yan, H., Bergner, A.J., Enomoto, H., Milbrandt, J., Newgreen, D.F., Young, H.M., Neural cells in the esophagus respond to glial cell line-derived neurotrophic factor and neurturin, and are RET-dependent. Dev. Biol. 272 (2004), 118–133.
