[en] The building of the brain is a multistep process that requires the coordinate expression of thousands of genes and an intense nucleocytoplasmic transport of RNA and proteins. This transport is mediated by karyopherins that comprise importins and exportins. Here, we investigated the role of the ss-importin, importin-8 (IPO8) during mouse cerebral corticogenesis as several of its cargoes have been shown to be essential during this process. First, we showed that Ipo8 mRNA is expressed in mouse brain at various embryonic ages with a clear signal in the sub-ventricular/ventricular zone (SVZ/VZ), the cerebral cortical plate (CP) and the ganglionic eminences. We found that acute knockdown of IPO8 in cortical progenitors reduced both their proliferation and cell cycle exit leading to the increase in apical progenitor pool without influencing the number of basal progenitors (BPs). Projection neurons ultimately reached their appropriate cerebral cortical layer, but their dendritogenesis was specifically affected, resulting in neurons with reduced dendrite complexity. IPO8 knockdown also slowed the migration of cortical interneurons. Together, our data demonstrate that IPO8 contribute to the coordination of several critical steps of cerebral cortex development. These results suggest that the impairment of IPO8 function might be associated with some diseases of neuronal migration defects.
Grisar, Thierry ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
de Nijs, Laurence
Lakaye, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Language :
English
Title :
Importin-8 Modulates Division of Apical Progenitors, Dendritogenesis and Tangential Migration During Development of Mouse Cortex.
Adam S. A., (2009). The nuclear transport machinery in Caenorhabditis elegans: a central role in morphogenesis. Semin. Cell Dev. Biol. 20, 576–581. 10.1016/j.semcdb.2009.03.01319577735.
Anderson S., Vanderhaeghen P., (2015). Cortical neurogenesis from pluripotent stem cells: complexity emerging from simplicity. Curr. Opin. Neurobiol. 27, 151–157. 10.1016/j.conb.2014.03.01224747604.
Ayoub A. E., Oh S., Xie Y., Leng J., Cotney J., Dominguez M. H.. (2011). Transcriptional programs in transient embryonic zones of the cerebral cortex de fi ned by high-resolution mRNA sequencing. Proc. Natl. Acad. Sci. U S A 108, 14950–14955. 10.1073/pnas.111221310821873192.
Bai J., Ramos R. L., Ackman J. B., Thomas A. M., Lee R. V., LoTurco J. J., (2003). RNAi reveals doublecortin is required for radial migration in rat neocortex. Nat. Neurosci. 6, 1277–1283. 10.1038/nn115314625554.
Bellion A., Baudoin J.-P., Alvarez C., Bornens M., Métin C., (2005). Nucleokinesis in tangentially migrating neurons comprises two alternating phases: forward migration of the golgi/centrosome associated with centrosome splitting and myosin contraction at the rear. J. Neurosci. 25, 5691–5699. 10.1523/JNEUROSCI.1030-05.200515958735.
Chou S.-J., O’Leary D. D. M., (2013). Role for Lhx2 in corticogenesis through regulation of progenitor differentiation. Mol. Cell. Neurosci. 56, 1–9. 10.1016/j.mcn.2013.02.00623454273.
Cubelos B., Sebastián-Serrano A., Beccari L., Calcagnotto M. E., Cisneros E., Kim S.. (2010). Cux1 and Cux2 regulate dendritic branching, spine morphology, and synapses of the upper layer neurons of the cortex. Neuron 66, 523–535. 10.1016/j.neuron.2010.04.03820510857.
Culjkovic B., Topisirovic I., Skrabanek L., Ruiz-Gutierrez M., Borden K. L. B., (2006). eIF4E is a central node of an RNA regulon that governs cellular proliferation. J. Cell Biol. 175, 415–426. 10.1083/jcb.20060702017074885.
Daviaud N., Chen K., Huang Y., Friedel R. H., Zou H., (2016). Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant. Dev. Neurobiol. 76, 882–899. 10.1002/dneu.2236426579598.
De Juan Romero C., Borrell V., (2015). Coevolution of radial glial cells and the cerebral cortex. Glia 63, 1303–1319. 10.1002/glia.2282725808466.
DeBoer E. M., Kraushar M. L., Hart R. P., Rasin M.-R., (2013). Post-transcriptional regulatory elements and spatiotemporal specification of neocortical stem cells and projection neurons. Neuroscience 248, 499–528. 10.1016/j.neuroscience.2013.05.04223727006.
de Nijs L., Wolkoff N., Coumans B., Delgado-escueta A. V., Grisar T., Lakaye B., (2012). Mutations of EFHC1, linked to juvenile myoclonic epilepsy, disrupt radial and tangential migrations during brain development. Hum. Mol. Genet. 21, 5106–5117. 10.1093/hmg/dds35622926142.
Doyle M., Badertscher L., Jaskiewicz L., Güttinger S., Jurado S., Hugenschmidt T.. (2013). The double-stranded RNA binding domain of human Dicer functions as a nuclear localization signal. RNA 19, 1238–1252. 10.1261/rna.039255.11323882114.
Dwyer X. N. D., Chen B., Chou X. S., Hippenmeyer X. S., Nguyen X. L., Ghashghaei X. H. T., (2016). Neural stem cells to cerebral cortex: emerging mechanisms regulating progenitor behavior and productivity. J. Neurosci. 36, 11394–11401. 10.1523/JNEUROSCI.2359-16.201627911741.
Englund C., Fink A., Lau C., Pham D., Daza R. A. M., Bulfone A.. (2005). Pax6, Tbr2, and Tbr1 Are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J. Neurosci. 25, 247–251. 10.1523/JNEUROSCI.2899-04.200515634788.
Faux C., Rakic S., Andrews W., Britto M. J., (2012). Neurons on the move: migration and lamination of cortical interneurons. Neurosignals 20, 168–189. 10.1159/00033448922572780.
Forwood J. K., Lange A., Zachariae U., Marfori M., Preast C., Grubmu H.. (2010). Quantitative structural analysis of importin-β flexibility: paradigm for solenoid protein structures. Structure 18, 1171–1183. 10.1016/j.str.2010.06.01520826343.
Freitas N., Cunha C., (2009). Mechanisms and signals for the nuclear import of proteins. Curr. Genomics 10, 550–557. 10.2174/13892020978950394120514217.
Honda T., Nakajima K., (2006). Mouse disabled1 (DAB1) is a nucleocytoplasmic shuttling protein. J. Biol. Chem. 281, 38951–38965. 10.1074/jbc.M60906120017062576.
Honda T., Nakajima K., (2016). Proper level of cytosolic disabled-1, which is regulated by dual nuclear translocation pathways, is important for cortical neuronal migration. Cereb. Cortex 26, 3219–3236. 10.1093/cercor/bhv16226209842.
Hoshiba X. Y., Toda T., Ebisu H., Wakimoto M., Yanagi S., Kawasaki H., (2016). Sox11 balances dendritic morphogenesis with neuronal migration in the developing cerebral cortex. J. Neurosci. 36, 5775–5784. 10.1523/JNEUROSCI.3250-15.201627225767.
Kawabe H., Neeb A., Dimova K., Young S. M., Jr. Takeda M., Katsurabayashi S.. (2010). Regulation of Rap2A by the ubiquitin ligase Nedd4–1 controls neurite development. Neuron 65, 358–372. 10.1016/j.neuron.2010.01.00720159449.
Lai K., Zhao Y., Ch’ng T. H., Martin K. C., (2008). Importin-mediated retrograde transport of CREB2 from distal processes to the nucleus in neurons. Proc. Natl. Acad. Sci. U S A 105, 17175–17180. 10.1073/pnas.080390610518957537.
Lee G. H., Kim S. H., Homayouni R., D’Arcangelo G., (2012). Dab2ip regulates neuronal migration and neurite outgrowth in the developing neocortex. PLoS One 7:e46592. 10.1371/journal.pone.004659223056358.
Lin T. V., Hsieh L., Kimura T., Malone T. J., Bordey A., (2016). Normalizing translation through 4E-BP prevents mTOR-driven cortical mislamination and ameliorates aberrant neuron integration. Proc. Natl. Acad. Sci. U S A 113, 11330–11335. 10.1073/pnas.160574011327647922.
Liu Y., Tsai J., Chen J., Yang W., Chang P., (2017). Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon. Sci. Rep. 7:42895. 10.1016/j.mod.2017.04.34728276447.
Lopez M. E., (2014). Combined in situ hybridization/immunohistochemistry (ISH/IH) on free-floating vibratome tissue sections. Bio Protoc. 4:e1243. 10.21769/bioprotoc.124327547787.
Luhmann H. J., Kirischuk S., Sinning A., Kilb W., (2014). Early GABAergic circuitry in the cerebral cortex. Curr. Opin. Neurobiol. 26, 72–78. 10.1016/j.conb.2013.12.01424434608.
Makihara H., Nakai S., Ohkubo W., Yamashita N., Kiyonari H., Shioi G.. (2016). CRMP1 and CRMP2 have synergistic but distinct roles in dendritic development. Genes Cells 21, 994–1005. 10.1111/gtc.1239927480924.
Martini F. J., Valdeolmillos M., (2010). Actomyosin contraction at the cell rear drives nuclear translocation in migrating cortical interneurons. J. Neurosci. 30, 8660–8670. 10.1523/JNEUROSCI.1962-10.201020573911.
Mosammaparast N., Pemberton L. F., (2004). Karyopherins: from nuclear-transport mediators to nuclear-function regulators. Trends Cell Biol. 14, 547–556. 10.1016/j.tcb.2004.09.00415450977.
Mosca T. J., Schwarz T. L., (2010). The nuclear import of Frizzled2-C by importins-β11 and α2 promotes postsynaptic development. Nat. Neurosci. 13, 935–943. 10.1038/nn.259320601947.
Nowakowski T. J., Mysiak K. S., Leary T. O., Fotaki V., Pratt T., Price D. J., (2013). Loss of functional Dicer in mouse radial glia cell-autonomously prolongs cortical neurogenesis. Dev. Biol. 382, 530–537. 10.1016/j.ydbio.2013.08.02324012747.
Oh J., Kwon A., Jo A., Kim H., Goo Y., Lee J.. (2013). Activity-dependent synaptic localization of processing bodies and their role in dendritic structural plasticity. J. Cell Sci. 126, 2114–2123. 10.3410/f.717989183.79347804523487039.
Olszewska M., Bujarski J. J., Kurpisz M., (2012). P-bodies and their functions during mRNA cell cycle: mini-review. Cell Biochem. Funct. 30, 177–182. 10.1002/cbf.280422249943.
O’Neill K. M., Akum B. F., Dhawan S. T., Kwon M., Langhammer C. G., Firestein B. L., (2015). Assessing effects on dendritic arborization using novel Sholl analyses. Front. Cell. Neurosci. 9:285. 10.3389/fncel.2015.0028526283921.
Pacal M., Bremner R., (2012). Mapping differentiation kinetics in the mouse retina reveals an extensive period of cell cycle protein expression in post-mitotic newborn neurons. Dev. Dyn. 241, 1525–1544. 10.1002/dvdy.2384022837015.
Perry R. B., Fainzilber M., (2009). Nuclear transport factors in neuronal function. Semin. Cell Dev. Biol. 20, 600–606. 10.1016/j.semcdb.2009.04.01419409503.
Peyre E., Silva C. G., Nguyen L., (2015). Crosstalk between intracellular and extracellular signals regulating interneuron production, migration and integration into the cortex. Front. Cell. Neurosci. 9:129. 10.3389/fncel.2015.0012925926769.
Puram S. V., Bonni A., (2013). Cell-intrinsic drivers of dendrite morphogenesis. Development 140, 4657–4671. 10.1242/dev.08767624255095.
Putker M., Vos H. R., van Dorenmalen K., de Ruiter H., Duran A. G., Snel B.. (2015). Evolutionary acquisition of cysteines determines FOXO paralog-specific redox signaling. Antioxid. Redox Signal. 22, 15–28. 10.1089/ars.2014.605625069953.
Quan Y., Ji Z., Wang X., Tartakoff A. M., Tao T., (2008). Evolutionary and transcriptional analysis of karyopherin β superfamily proteins*. Mol. Cell. Proteomics 7, 1254–1269. 10.1074/mcp.M700511-mcp20018353765.
Ross J. P., Kassir Z., (2014). The varied roles of nuclear argonaute-small RNA complexes and avenues for therapy. Mol. Ther. Nucleic Acids 3:e203. 10.1038/mtna.2014.5425313622.
Ross S. E., Greenberg M. E., Stiles C. D., (2003). Basic helix-loop-helix factors in cortical development. Neuron 39, 13–25. 10.1016/s0896-6273(03)00365-912848929.
Sessa A., Mao C., Hadjantonakis A.-K., Klein W. H., Broccoli V., (2008). Tbr2 directs conversion of radial glia into basal precursors and guides neuronal amplification by indirect neurogenesis in the developing neocortex. Neuron 60, 56–69. 10.1016/j.neuron.2008.09.02818940588.
Shmidt T., Hampich F., Ridders M., Schultrich S., Hans V. H., Tenner K.. (2007). Normal brain development in importin-α5 deficient-mice. Nat. Cell Biol. 9, 1337–1338. 10.1038/ncb1207-133718059353.
Simon-Areces J., Acaz-Fonseca E., Ruiz-Palmero I., Garcia-Segura L. M., Arevalo M. A., (2013). A CRM1-mediated nuclear export signal is essential for cytoplasmic localization of neurogenin 3 in neurons. PLoS One 8:e55237. 10.1371/journal.pone.005523723383123.
Søes S., Sørensen B. S., Alsner J., Overgaard J., Hager H., Hansen L. L.. (2013). Identification of accurate reference genes for RT-qPCR analysis of formalin-fixed paraffin-embedded tissue from primary Non-Small Cell Lung Cancers and brain and lymph node metastases. Lung Cancer 81, 180–186. 10.1016/j.lungcan.2013.04.00723643276.
Sun Y., Fei T., Yang T., Zhang F., Chen Y., Li H.. (2010). The suppression of CRMP2 expression by bone morphogenetic protein (BMP) -SMAD gradient signaling controls multiple stages of neuronal development*. J. Biol. Chem. 285, 39039–39050. 10.1074/jbc.M110.16835120926379.
Tanaka D., Nakaya Y., Yanagawa Y., Obata K., Murakami F., (2003). Multimodal tangential migration of neocortical GABAergic neurons independent of GPI-anchored proteins. Development 130, 5803–5813. 10.1242/dev.0082514534141.
Telley L., Govindan S., Prados J., Stevant I., Nef S., Dermitzakis E.. (2016). Sequential transcriptional waves direct the differentiation of newborn neurons in the mouse neocortex. Science 351, 1443–1446. 10.1126/science.aad836126940868.
Tichopad A., Dilger M., Schwarz G., Pfaffl M. W., (2003). Standardized determination of real-time PCR efficiency from a single reaction set-up. Nucleic Acids Res. 31:e122. 10.1093/nar/gng12214530455.
Ting C., Herman T., Yonekura S., Gao S., Wang J., Serpe M.. (2007). Tiling of R7 axons in the Drosophila visual system is mediated both by transduction of an activin signal to the nucleus and by mutual repulsion. Neuron 56, 793–806. 10.1016/j.neuron.2007.09.03318054857.
Tsai J., Chen Y., Kriegstein A. R., Vallee R. B., (2005). LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. J. Cell Biol. 170, 935–945. 10.1083/jcb.20050516616144905.
Volpon L., Culjkovic-Kraljacic B., Osborne M. J., Ramteke A., Sun Q., Niesman A.. (2016). Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E. Proc. Natl. Acad. Sci. U S A 113, 5263–5268. 10.1073/pnas.152429111327114554.
Wachi T., Cornell B., Marshall C., Zhukarev V., Baas P. W., Toyo-oka K., (2016). Ablation of the 14–3-3γ protein results in neuronal migration delay and morphological defects in the developing cerebral cortex. Dev. Neurobiol. 76, 600–614. 10.1002/dneu.2233526297819.
Weinmann L., Höck J., Ivacevic T., Ohrt T., Mütze J., Schwille P.. (2009). Importin 8 is a gene silencing factor that targets argonaute proteins to distinct mRNAs. Cell 136, 496–507. 10.1016/j.cell.2008.12.02319167051.
Wilson M. D., Sethi S., Lein P. J., Keil K. P., (2017). Valid statistical approaches for analyzing sholl data: mixed effects versus simple linear models. J. Neurosci. Methods 279, 33–43. 10.1016/j.jneumeth.2017.01.00328104486.
Yao X., Chen X., Cottonham C., Xu L., (2008). Preferential utilization of Imp7/8 in nuclear import of Smads. J. Biol. Chem. 283, 22867–22874. 10.1074/jbc.M80132020018519565.
Yasuhara N., Shibazaki N., Tanaka S., Nagai M., Kamikawa Y., Oe S.. (2007). Triggering neural differentiation of ES cells by subtype switching of importin-α. Nat. Cell Biol. 9, 72–79. 10.1038/ncb152117159997.
Young J. C., Major A. T., Miyamoto Y., Loveland K. L., Jans D. A., (2011). Distinct effects of importin a-2 and a-4 on Oct3/4 localization and expression in mouse embryonic stem cells. FASEB J. 25, 3958–3965. 10.1096/fj.10-17694121840941.
Zechel S., Nakagawa Y., Iba C. F., States U., (2016). Thalamo-cortical axons regulate the radial dispersion of neocortical GABAergic interneurons. Elife 5:e20770. 10.7554/elife.2077027935475.
Zhang J., Ma W., Tian S., Fan Z., Ma X., Yang X.. (2014). RanBPM interacts with TβRI, TRAF6 and curbs TGF induced nuclear accumulation of TβRI. Cell. Signal. 26, 162–172. 10.1016/j.cellsig.2013.09.01924103590.
Zhang Y., Ueno Y., Liu X. S., Buller B., Wang X., Chopp M.. (2013). The microRNA-17–92 cluster enhances axonal outgrowth in embryonic cortical neurons. J. Neurosci. 33, 6885–6894. 10.1523/JNEUROSCI.5180-12.201323595747.