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FoxP2 protein levels regulate cell morphology changes and migration patterns in the vertebrate developing telencephalon

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Abstract

In the mammalian telencephalon, part of the progenitor cells transition from multipolar to bipolar morphology as they invade the mantle zone. This associates with changing patterns of radial migration. However, the molecules implicated in these morphology transitions are not well known. In the present work, we analyzed the function of FoxP2 protein in this process during telencephalic development in vertebrates. We analyzed the expression of FoxP2 protein and its relation with cell morphology and migratory patterns in mouse and chicken developing striatum. We observed FoxP2 protein expressed in a gradient from the subventricular zone to the mantle layer in mice embryos. In the FoxP2 low domain cells showed multipolar migration. In the striatal mantle layer where FoxP2 protein expression is higher, cells showed locomoting migration and bipolar morphology. In contrast, FoxP2 showed a high and homogenous expression pattern in chicken striatum, thus bipolar morphology predominated. Elevation of FoxP2 in the striatal subventricular zone by in utero electroporation promoted bipolar morphology and impaired multipolar radial migration. In mouse cerebral cortex we obtained similar results. FoxP2 promotes transition from multipolar to bipolar morphology by means of gradiental expression in mouse striatum and cortex. Together these results indicate a role of FoxP2 differential expression in cell morphology control of the vertebrate telencephalon.

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References

  • Bhide PG (1996) Cell cycle kinetics in the embryonic mouse cor- of a neuron-specific beta-tubulin isotype during chick embryogenepus striatum. J Comp Neurol 374:506–522

    Article  CAS  PubMed  Google Scholar 

  • Bielle F, Marcos-Mondejar P, Keita M, Mailhes C, Verney C et al (2011) Slit2 activity in the migration of guidepost neurons shapes thalamic projections during development and evolution. Neuron 69:1085–1098

    Article  CAS  PubMed  Google Scholar 

  • Campbell P, Reep RL, Stoll ML, Ophir AG, Phelps SM (2009) Conservation and diversity of Foxp2 expression in muroid rodents: functional implications. J Comp Neurol 512:84–100

    Article  PubMed  PubMed Central  Google Scholar 

  • Carri AD, Onorati M, Lelos MJ, Castiglioni V, Faedo A et al (2013) Developmentally coordinated extrinsic signals drive human pluripotent stem cell differentiation toward authentic DARPP-32+ medium-sized spiny neurons. Development 140:301–312

    Article  CAS  Google Scholar 

  • Charvet CJ, Owerkowicz T, Striedter GF (2009) Phylogeny of the telencephalic subventricular zone in sauropsids: evidence for the sequential evolution of pallial and subpallial subventricular zones. Brain Behav Evol 73:285–294

    Article  PubMed  Google Scholar 

  • Chiu YC, Li MY, Liu YH, Ding JY, Yu JY et al (2014) Foxp2 regulates neuronal differentiation and neuronal subtype specification. Dev Neurobiol 74:723–738

    Article  CAS  PubMed  Google Scholar 

  • Clovis YM, Enard W, Marinaro F, Huttner WB, De Pietri Tonelli D (2012) Convergent repression of Foxp2 3′UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons. Development 139:3332–3342

    Article  CAS  PubMed  Google Scholar 

  • Feng Y, Walsh CA (2001) Protein-protein interactions, cytoskeletal regulation and neuronal migration. Nat Rev Neurosci 2:408–416

    Article  CAS  PubMed  Google Scholar 

  • Ferland RJ, Cherry TJ, Preware PO, Morrisey EE, Walsh CA (2003) Characterization of Foxp2 and Foxp1 mRNA and protein in the developing and mature brain. J Comp Neurol 460:266–279

    Article  CAS  PubMed  Google Scholar 

  • García-Calero E, Puelles L (2009) Enc1 expression in the chick telencephalon at intermediate and late stages of development. J Comp Neurol 517:564–580

    Article  PubMed  Google Scholar 

  • Gleeson JG, Walsh CA (2000) Neuronal migration disorders: from genetic diseases to developmental mechanisms. Trends Neurosci 23:352–359

    Article  CAS  PubMed  Google Scholar 

  • Haesler S, Wada K, Nshdejan A, Morrisey EE, Lints T et al (2004) FoxP2 expression in avian vocal learners and non-learners. J Neurosci 24:3164–3175

    Article  CAS  PubMed  Google Scholar 

  • Hirotsune S, Fleck MW, Gambello MJ, Bix GJ, Chen A et al (1998) Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality. Nat Genet 19:333–339

    Article  CAS  PubMed  Google Scholar 

  • Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP (2001) A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413:519–523

    Article  CAS  PubMed  Google Scholar 

  • Matsuda T, Cepko CL (2004) Electroporation and RNA interference in the rodent retina in vivo and in vitro. Proc Natl Acad Sci USA 101:16–22

    Article  CAS  PubMed  Google Scholar 

  • Nadarajah B, Brunstrom JE, Grutzendler J, Wong RO, Pearlman AL (2001) Two modes of radial migration in early development of the cerebral cortex. Nat Neurosci 4:143–150

    Article  CAS  PubMed  Google Scholar 

  • Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7:136–144

    Article  CAS  PubMed  Google Scholar 

  • Pilz GA, Shitamukai A, Reillo I, Pacary E, Schwausch J et al (2013) Amplification of progenitors in the mammalian telencephalon includes a new radial glial cell type. Nat Commun 4:2125

    Article  PubMed  PubMed Central  Google Scholar 

  • Rakic P (1972) Mode of cell migration to the superficial layers of fetal monkey neocortex. J Comp Neurol 145:61–83

    Article  CAS  PubMed  Google Scholar 

  • Rochefort C, He X, Scotto-Lomassese S, Scharff C (2007) Recruitment of FoxP2-expressing neurons to area X varies during song development. Dev Neurobiol 67:809–817

    Article  CAS  PubMed  Google Scholar 

  • Rousso DL, Pearson CA, Gaber ZB, Miquelajauregui A, Li S, Portera-Cailliau C (2012) Foxp-mediated suppression of N-cadherin regulates neuroepithelial character and progenitor maintenance in the CNS. Neuron 74:314–330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulz SB, Haesler S, Scharff C, Rochefort C (2010) Knockdown of FoxP2 alters spine density in Area X of the zebra finch. Genes Brain Behav 9:732–740

    Article  CAS  PubMed  Google Scholar 

  • Scott BB, Gardner T, Ji N, Fee MS, Lois C (2012) Wandering neuronal migration in the postnatal vertebrate forebrain. J Neurosci 32:1436–1446

    Article  CAS  PubMed  Google Scholar 

  • Spiteri E, Konopka G, Coppola G, Bomar J, Oldham M et al (2007) Identification of the transcriptional targets of FOXP2, a gene linked to speech and language, in developing human brain. Am J Hum Genet 81:1144–1157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Takahashi K, Liu FC, Hirokawa K, Takahashi H (2003) Expression of Foxp2, a gene involved in speech and language, in the developing and adult striatum. J Neurosci Res 73:61–72

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Liu FC, Hirokawa K, Takahashi H (2008) Expression of Foxp4 in the developing and adult rat forebrain. J Neurosci Res 86:3106–3116

    Article  CAS  PubMed  Google Scholar 

  • Teramitsu I, Kudo LC, London SE, Geschwind DH, White SA (2004) Parallel FoxP1 and FoxP2 expression in songbird and human brain predicts functional interaction. J Neurosci 24:3152–3163

    Article  CAS  PubMed  Google Scholar 

  • Tsai JW, Chen Y, Kriegstein AR, Vallee RB (2005) LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages. J Cell Biol 170:935–945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsui D, Vessey JP, Tomita H, Kaplan DR, Miller FD (2013) FoxP2 regulates neurogenesis during embryonic cortical development. J Neurosci 33:244–258

    Article  CAS  PubMed  Google Scholar 

  • Vernes SC, Oliver PL, Spiteri E, Lockstone HE, Puliyadi R et al (2007) Highthroughput analysis of promoter occupancy reveals direct neural targets of FOXP2, a gene mutated in speech and language disorders. Am J Hum Genet 81:1232–1250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vernes SC, Spiteri E, Nicod J, Groszer M, Taylor JM et al (2011) Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain. PLoS Genet 7:e1002145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Watkins KE, Vargha-Khadem F, Ashburner J, Passingham RE, Connelly A et al (2002) MRI analysis of an inherited speech and language disorder: structural brain abnormalities. Brain 125:465–478

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank gratefully P. Almagro and J.E. Martínez-López for the technical support. We thank Dr. MA Nieto for the pCX-GFP plasmid. This work was supported by Spanish Ministry of Science and Innovation Grant BFU-2011-27326, Institute of Health Carlos III, Spanish Cell Therapy Network and Research Center of Mental Health (RD06/0010/0023; RD12/0019/0024), General Council of Valencia (Prometeo 2009/028 and 11/2011/042). E.G.C. was supported by the Postdoctoral Program of the “Consejo Superior de Investigaciones Científicas-Junta de Ampliación de Estudios.”

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Correspondence to Elena Garcia-Calero.

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Garcia-Calero, E., Botella-Lopez, A., Bahamonde, O. et al. FoxP2 protein levels regulate cell morphology changes and migration patterns in the vertebrate developing telencephalon. Brain Struct Funct 221, 2905–2917 (2016). https://doi.org/10.1007/s00429-015-1079-7

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  • DOI: https://doi.org/10.1007/s00429-015-1079-7

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