リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「マウス側脳室脈絡叢からのSonic hedgehogの分泌が側脳室脈絡叢の肥大と大脳新皮質表面積の拡大をもたらす」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

マウス側脳室脈絡叢からのSonic hedgehogの分泌が側脳室脈絡叢の肥大と大脳新皮質表面積の拡大をもたらす

木下, 晃 京都大学 DOI:10.14989/doctor.k24047

2022.03.23

概要

哺乳類の大脳新皮質の発生は、単層の神経幹細胞のシートから始まり、神経幹細胞が細胞分裂と分化を繰り返すことで最終的に6層からなる神経回路を形成する。この大脳新皮質発生のプロセスは哺乳類間でほとんど共通と考えられている。ヒトやサルといった霊長類の脳は、齧歯類と比べると非常に拡大した、しわのある大脳新皮質をもち、より高い知能と認知能力の獲得につながったと考えられている。しかし大脳新皮質の拡大を生むメカニズムについては未だ明らかになっていない。これまで霊長類の大脳新皮質拡大について神経幹細胞の内的因子に着目した研究が多数報告されているが、申請者は神経幹細胞の外的因子である脳脊髄液と、その分泌源である脈絡叢に着目した。脈絡叢は脳脊髄液の約8割を分泌する組織であり、成体脳の恒常性の維持に寄与している。加えて近年では、脈絡叢より分泌される様々なシグナル分子が脳発生過程の神経幹細胞の制御に関与していることが明らかになっている。また、脳脊髄液によって形成される脳室内の圧力も、大脳の形態形成や神経幹細胞の分裂に影響を与えることが知られている。興味深いことに、霊長類と齧歯類の脳の発生過程を比較すると、霊長類胎仔の脳では側脳室脈絡叢がより顕著に発達していることが報告されている。脈絡叢の発達は、脳脊髄液分泌量の増加による脳室内圧の増加や、シグナル分子の分泌量の増加を起こし得ることから、大脳新皮質の拡大に関与する可能性が考えられた。しかし、大脳の発生過程における、脈絡叢分泌因子の機能解析や、側脳室脈絡叢肥大を誘導する分子については、未だ十分に調べられていない。

そこで申請者は、側脳室脈絡叢の拡大やシグナル分子分泌の人為的改変を目的として、脈絡叢前駆細胞や脈絡叢上皮細胞に特異的に遺伝子発現操作を可能にする遺伝子組換えマウス (pTtr-rtTA と pFuguOtx2-rtTA)を作製した。これらの Tet-on システムを用いた遺伝子改変モデルマウスにおいて、 発生過程 の脈絡叢より Sonic hedgehog(Shh) を強制発現させた。Shhはマウスの脳の発生過程において、第四脳室脈絡叢で発現しており、第四脳室脈絡叢の伸長や血管新生に重要であることが知られているが、マウス側脳室脈絡叢ではShhの発現が報告されていない。また、ヒト胎児側脳室脈絡叢ではShhの発現と分泌が報告されている。pTtr-rtTAを用いてShhを側脳室脈絡叢で強制発現させることにより、マウス胎仔脳で脈絡叢前駆細胞の分裂の増加や、脈絡叢の拡大、分枝数の顕著な増加を観察できた。また脈絡叢から分泌されたShhが大脳新皮質の神経幹細胞の分化を抑制し、増殖を促進したことで、脳室および脳室帯の拡大とともに大脳表面積の拡大及び、しわの形成が認められた。これらの結果は発生過程の脈絡叢からのShhの分泌増加が、霊長類特有の側脳室脈絡叢の肥大化や大脳新皮質の拡大といった、哺乳類大脳の進化に関与している可能性が示唆される。また近年では、成体脳における脈絡叢による成体神経幹細胞や神経活動の制御にも注目が集まっている。しかしpTtr-rtTAは他の臓器での非特異的な発現や、発達が進むごとに発現が低下する特性などから、成体脳での遺伝子発現の誘導には適さない。そこで申請者はフグ(学名Fugurubripes;トラフグ)のOtx2遺伝子発現調節領域(pFugu)を用いて、pFuguOtx2-rtTA遺伝子組換えマウスを作製し、成体脳での側脳室脈絡叢のシグナル分子分泌の人為的操作を試みた。pFuguOtx2-rtTA遺伝子組換えマウスを用いて成体脳でShhを強制発現させたところ、脳室下帯における神経幹細胞の分裂と神経新生の増加や、嗅球での新生神経細胞の組み込みの増加が観察された。pFuguOtx2-rtTA遺伝子組換えマウスは成体脳における脈絡叢分泌因子の機能解析に用いることができると考えられる。

本研究により、脳発生過程における側脳室脈絡叢でのShhの発現・分泌が、哺乳類大脳の進化において重要な役割を果たした可能性が示された。また、申請者の開発した pFuguOtx2-rtTA 遺伝子組換えマウスを用いることで、脈絡叢分泌因子が成体脳の構造機能に及ぼす影響の解析や、脈絡叢機能の改変の研究などの応用展開が期待できる。

この論文で使われている画像

参考文献

1. Alex A. Pollen, Tomasz J. Nowakowski, Jiadong Chen, Hanna Retallack,Carmen Sandoval-Espinosa, Cory R. Nicholas, Joe Shuga, Siyuan J. Liu,Michael C. Oldham, Aaron Diaz, Daniel A. Lim, Anne A. Leyrat, Jay A. West,Arnold R. Kriegstein. Molecular Identity of Human Outer Radial Glia DuringCortical Development. Cell. 2015 Sep 24;163(1):55-67.

2. Anthony TE, Klein C, Fishell G, Heintz N. Radial glia serve as neuronalprogenitors in all regions of the central nervous system. Neuron. 2004 Mar25;41(6):881-90. doi: 10.1016/s0896-6273(04)00140-0. PMID: 15046721.

3. Bayer SA, Altman J, Russo RJ, Zhang X. Timetables of neurogenesis in thehuman brain based on experimentally determined patterns in the rat.Neurotoxicology. 1993 Spring;14(1):83-144. PMID: 8361683.

4. Bryniarski MA, Ren T, Rizvi AR, Snyder AM, Morris ME. Targeting the ChoroidPlexuses for Protein Drug Delivery. Pharmaceutics. 2020 Oct 14;12(10):963. doi:10.3390/pharmaceutics12100963. PMID: 33066423; PMCID: PMC7602164.

5. Castañeyra-Ruiz L, González-Marrero I, Hernández-Abad LG, Carmona-CaleroEM, Meyer G, Castañeyra-Perdomo A. A Distal to Proximal Gradient of HumanChoroid Plexus Development, with Antagonistic Expression of Glut1 and AQP1in Mature Cells vs. Calbindin and PCNA in Proliferative Cells. FrontNeuroanat. 2016 Sep 23;10:87. doi: 10.3389/fnana.2016.00087. PMID:27721744; PMCID: PMC5034118.

6. Chizhikov VV, Iskusnykh IY, Steshina EY, Fattakhov N, Lindgren AG, ShettyAS, Roy A, Tole S, Millen KJ. Early dorsomedial tissue interactions regulategyrification of distal neocortex. Nat Commun. 2019 Nov 15;10(1):5192. doi:10.1038/s41467-019-12913-z. PMID: 31729356; PMCID: PMC6858446.

7. Christensen IB, Gyldenholm T, Damkier HH, Praetorius J. Polarization ofmembrane associated proteins in the choroid plexus epithelium from normaland slc4a10 knockout mice. Front Physiol. 2013 Nov 27;4:344. doi:10.3389/fphys.2013.00344. PMID: 24348423; PMCID: PMC3842056.

8. Clancy B, Darlington RB, Finlay BL. Translating developmental time acrossmammalian species. Neuroscience. 2001;105(1):7-17. doi:10.1016/s0306-4522(01)00171-3. PMID: 11483296.

9. Costa RH, Lai E, Darnell JE Jr. Transcriptional control of the mouseprealbumin (transthyretin) gene: both promoter sequences and a distinctenhancer are cell specific. Mol Cell Biol. 1986 Dec;6(12):4697-708. doi:10.1128/mcb.6.12.4697-4708.1986. PMID: 3025666; PMCID: PMC367255.

10. Costa RH, Van Dyke TA, Yan C, Kuo F, Darnell JE Jr. Similarities intransthyretin gene expression and differences in transcription factors: liver andyolk sac compared to choroid plexus. Proc Natl Acad Sci U S A. 1990Sep;87(17):6589-93. doi: 10.1073/pnas.87.17.6589. PMID: 2395861; PMCID:PMC54582.

11. Costa RH, Grayson DR. Site-directed mutagenesis of hepatocyte nuclear factor(HNF) binding sites in the mouse transthyretin (TTR) promoter revealsynergistic interactions with its enhancer region. Nucleic Acids Res. 1991 Aug11;19(15):4139-45. doi: 10.1093/nar/19.15.4139. PMID: 1870969; PMCID:PMC328553.

12. Crouthamel MH, Kelly EJ, Ho RJ. Development and characterization oftransgenic mouse models for conditional gene knockout in the blood-brain andblood-CSF barriers. Transgenic Res. 2012 Feb;21(1):113-30. doi:10.1007/s11248-011-9512-z. Epub 2011 May 3. PMID: 21538071; PMCID:PMC3192922.

13. Damkier HH, Brown PD, Praetorius J. Cerebrospinal fluid secretion by thechoroid plexus. Physiol Rev. 2013 Oct;93(4):1847-92. doi:10.1152/physrev.00004.2013. PMID: 24137023.

14. Dandy WE. EXTIRPATION OF THE CHOROID PLEXUS OF THE LATERALVENTRICLES IN COMMUNICATING HYDROCEPHALUS. Ann Surg. 1918Dec;68(6):569-79. doi: 10.1097/00000658-191812000-00001. PMID: 17864025;PMCID: PMC1427121.

15. Dani N, Herbst RH, McCabe C, Green GS, Kaiser K, Head JP, Cui J, Shipley FB,Jang A, Dionne D, Nguyen L, Rodman C, Riesenfeld SJ, Prochazka J,Prochazkova M, Sedlacek R, Zhang F, Bryja V, Rozenblatt-Rosen O, Habib N,Regev A, Lehtinen MK. A cellular and spatial map of the choroid plexus acrossbrain ventricles and ages. Cell. 2021 May 27;184(11):3056-3074.e21. doi:10.1016/j.cell.2021.04.003. Epub 2021 Apr 30. PMID: 33932339; PMCID:PMC8214809.

16. Del Toro D, Ruff T, Cederfjäll E, Villalba A, Seyit-Bremer G, Borrell V, Klein R.Regulation of Cerebral Cortex Folding by Controlling Neuronal Migration viaFLRT Adhesion Molecules. Cell. 2017 May 4;169(4):621-635.e16. doi:10.1016/j.cell.2017.04.012. PMID: 28475893.

17. Desmond ME, Jacobson AG. Embryonic brain enlargement requirescerebrospinal fluid pressure. Dev Biol. 1977 May;57(1):188-98. doi:10.1016/0012-1606(77)90364-5. PMID: 863106.

18. Ek CJ, Nathanielsz P, Li C, Mallard C. Transcriptomal changes and functionalannotation of the developing non-human primate choroid plexus. FrontNeurosci. 2015 Mar 12;9:82. doi: 10.3389/fnins.2015.00082. PMID: 25814924;PMCID: PMC4357249.

19. Eze UC, Bhaduri A, Haeussler M, Nowakowski TJ, Kriegstein AR. Single-cellatlas of early human brain development highlights heterogeneity of humanneuroepithelial cells and early radial glia. Nat Neurosci. 2021Apr;24(4):584-594. doi: 10.1038/s41593-020-00794-1. Epub 2021 Mar 15. PMID:33723434; PMCID: PMC8012207.

20. Fiddes IT, Lodewijk GA, Mooring M, Bosworth CM, Ewing AD, Mantalas GL,Novak AM, van den Bout A, Bishara A, Rosenkrantz JL, Lorig-Roach R, FieldAR, Haeussler M, Russo L, Bhaduri A, Nowakowski TJ, Pollen AA, DoughertyML, Nuttle X, Addor MC, Zwolinski S, Katzman S, Kriegstein A, Eichler EE,Salama SR, Jacobs FMJ, Haussler D. Human-Specific NOTCH2NL GenesAffect Notch Signaling and Cortical Neurogenesis. Cell. 2018 May31;173(6):1356-1369.e22. doi: 10.1016/j.cell.2018.03.051. Epub 2018 May 31.PMID: 29856954; PMCID: PMC5986104.

21. Fleischer V, Gonzalez-Escamilla G, Ciolac D, Albrecht P, Küry P, Gruchot J,Dietrich M, Hecker C, Müntefering T, Bock S, Oshaghi M, Radetz A, Cerina M,Krämer J, Wachsmuth L, Faber C, Lassmann H, Ruck T, Meuth SG,Muthuraman M, Groppa S. Translational value of choroid plexus imaging fortracking neuroinflammation in mice and humans. Proc Natl Acad Sci U S A.2021 Sep 7;118(36):e2025000118. doi: 10.1073/pnas.2025000118. PMID:34479997; PMCID: PMC8433504.

22. Florio M, Albert M, Taverna E, Namba T, Brandl H, Lewitus E, Haffner C,Sykes A, Wong FK, Peters J, Guhr E, Klemroth S, Prüfer K, Kelso J, NaumannR, Nüsslein I, Dahl A, Lachmann R, Pääbo S, Huttner WB. Human-specificgene ARHGAP11B promotes basal progenitor amplification and neocortexexpansion. Science. 2015 Mar 27;347(6229):1465-70. doi:10.1126/science.aaa1975. Epub 2015 Feb 26. PMID: 25721503.

23. Gage FH. Mammalian neural stem cells. Science. 2000 Feb 25;287(5457):1433-8.doi: 10.1126/science.287.5457.1433. PMID: 10688783.

24. Garcia KE, Okamoto RJ, Bayly PV, Taber LA. Contraction andstress-dependent growth shape the forebrain of the early chicken embryo. JMech Behav Biomed Mater. 2017 Jan;65:383-397. doi:10.1016/j.jmbbm.2016.08.010. Epub 2016 Aug 15. PMID: 27639481; PMCID:PMC5260613.

25. Garcia KE, Stewart WG, Espinosa MG, Gleghorn JP, Taber LA. Molecular andmechanical signals determine morphogenesis of the cerebral hemispheres inthe chicken embryo. Development. 2019 Oct 11;146(20):dev174318. doi:10.1242/dev.174318. PMID: 31604710; PMCID: PMC6826035.

26. Gertz CC, Kriegstein AR. Neuronal Migration Dynamics in the DevelopingFerret Cortex. J Neurosci. 2015 Oct 21;35(42):14307-15. doi:10.1523/JNEUROSCI.2198-15.2015. PMID: 26490868; PMCID: PMC4683689

27. Glickstein SB, Monaghan JA, Koeller HB, Jones TK, Ross ME. Cyclin D2 iscritical for intermediate progenitor cell proliferation in the embryonic cortex. JNeurosci. 2009 Jul 29;29(30):9614-24. doi: 10.1523/JNEUROSCI.2284-09.2009.PMID: 19641124; PMCID: PMC2811167.

28. Götz M, Huttner WB. The cell biology of neurogenesis. Nat Rev Mol Cell Biol.2005 Oct;6(10):777-88. doi: 10.1038/nrm1739. PMID: 16314867.

29. Hansen DV, Lui JH, Parker PR, Kriegstein AR. Neurogenic radial glia in theouter subventricular zone of human neocortex. Nature. 2010 Mar25;464(7288):554-561. doi: 10.1038/nature08845. PMID: 20154730.

30. Herculano-Houzel S. The human brain in numbers: a linearly scaled-upprimate brain. Front Hum Neurosci. 2009 Nov 9;3:31. doi:10.3389/neuro.09.031.2009. PMID: 19915731; PMCID: PMC2776484.

31. Hilgetag CC, Barbas H. Role of mechanical factors in the morphology of theprimate cerebral cortex. PLoS Comput Biol. 2006 Mar;2(3):e22. doi:10.1371/journal.pcbi.0020022. Epub 2006 Mar 24. PMID: 16557292; PMCID:PMC1409812.

32. Himmelstein DS, Bi C, Clark BS, Bai B, Kohtz JD. Balanced Shh signaling isrequired for proper formation and maintenance of dorsal telencephalic midlinestructures. BMC Dev Biol. 2010 Nov 29;10:118. doi: 10.1186/1471-213X-10-118.PMID: 21114856; PMCID: PMC3018372.

33. Huang X, Litingtung Y, Chiang C. Ectopic sonic hedgehog signaling impairstelencephalic dorsal midline development: implication for humanholoprosencephaly. Hum Mol Genet. 2007 Jun 15;16(12):1454-68. doi:10.1093/hmg/ddm096. Epub 2007 Apr 27. PMID: 17468181.

34. Huang X, Ketova T, Fleming JT, Wang H, Dey SK, Litingtung Y, Chiang C.Sonic hedgehog signaling regulates a novel epithelial progenitor domain of thehindbrain choroid plexus. Development. 2009 Aug;136(15):2535-43. doi:10.1242/dev.033795. Epub 2009 Jul 1. PMID: 19570847; PMCID: PMC2709062.

35. Huang X, Liu J, Ketova T, Fleming JT, Grover VK, Cooper MK, Litingtung Y,Chiang C. Transventricular delivery of Sonic hedgehog is essential to cerebellarventricular zone development. Proc Natl Acad Sci U S A. 2010 May4;107(18):8422-7. doi: 10.1073/pnas.0911838107. Epub 2010 Apr 16. PMID:20400693; PMCID: PMC2889567.

36. Hubert V, Dumot C, Ong E, Amaz C, Canet-Soulas E, Chauveau F, Wiart M.MRI coupled with clinically-applicable iron oxide nanoparticles reveals choroidplexus involvement in a murine model of neuroinflammation. Sci Rep. 2019 Jul11;9(1):10046. doi: 10.1038/s41598-019-46566-1. PMID: 31296913; PMCID:PMC6624288.

37. Imayoshi I, Shimogori T, Ohtsuka T, Kageyama R. Hes genes and neurogeninregulate non-neural versus neural fate specification in the dorsal telencephalicmidline. Development. 2008 Aug;135(15):2531-41. doi: 10.1242/dev.021535.Epub 2008 Jun 25. PMID: 18579678.

38. Inagaki T, Schoenwolf GC, Walker ML. Experimental model: change in theposterior fossa with surgically induced spina bifida aperta in mouse. PediatrNeurosurg. 1997 Apr;26(4):185-9. doi: 10.1159/000121188. PMID: 9436828.

39. Jan H. Lui, Tomasz J. Nowakowski, Alex A. Pollen, Ashkan Javaherian, ArnoldR. Kriegstein and Michael C. Oldham. Radial glia require PDGFD/PDGFRßsignaling in human but not mouse neocortex. Nature. 2014 Nov13;515(7526):264-8.

40. Janssen SF, van der Spek SJ, Ten Brink JB, Essing AH, Gorgels TG, van derSpek PJ, Jansonius NM, Bergen AA. Gene expression and functionalannotation of the human and mouse choroid plexus epithelium. PLoS One. 2013Dec 31;8(12):e83345. doi: 10.1371/journal.pone.0083345. PMID: 24391755;PMCID: PMC3877019.

41. Johansson PA, Irmler M, Acampora D, Beckers J, Simeone A, Götz M. Thetranscription factor Otx2 regulates choroid plexus development and function.Development. 2013 Mar;140(5):1055-66. doi: 10.1242/dev.090860. Epub 2013Jan 30. PMID: 23364326.

42. Johansson PA. The choroid plexuses and their impact on developmentalneurogenesis. Front Neurosci. 2014 Oct 24;8:340. doi: 10.3389/fnins.2014.00340.PMID: 25386116; PMCID: PMC4208491.

43. Johnson BA, Coutts M, Vo HM, Hao X, Fatima N, Rivera MJ, Sims RJ, Neel MJ,Kang YJ, Monuki ES. Accurate, strong, and stable reporting of choroid plexusepithelial cells in transgenic mice using a human transthyretin BAC. FluidsBarriers CNS. 2018 Aug 16;15(1):22. doi: 10.1186/s12987-018-0107-4. PMID:30111340; PMCID: PMC6094443.

44. Karimy JK, Duran D, Hu JK, Gavankar C, Gaillard JR, Bayri Y, Rice H,DiLuna ML, Gerzanich V, Marc Simard J, Kahle KT. Cerebrospinal fluidhypersecretion in pediatric hydrocephalus. Neurosurg Focus. 2016Nov;41(5):E10. doi: 10.3171/2016.8.FOCUS16278. PMID: 27798982.

45. Kimura C, Takeda N, Suzuki M, Oshimura M, Aizawa S, Matsuo I. Cis-actingelements conserved between mouse and pufferfish Otx2 genes govern theexpression in mesencephalic neural crest cells. Development. 1997Oct;124(20):3929-41. PMID: 9374391.

46. Kimura C, Yoshinaga K, Tian E, Suzuki M, Aizawa S, Matsuo I. Visceralendoderm mediates forebrain development by suppressing posteriorizingsignals. Dev Biol. 2000 Sep 15;225(2):304-21. doi: 10.1006/dbio.2000.9835.PMID: 10985852.

47. Kimura-Yoshida C, Kitajima K, Oda-Ishii I, Tian E, Suzuki M, Yamamoto M,Suzuki T, Kobayashi M, Aizawa S, Matsuo I. Characterization of the pufferfishOtx2 cis-regulators reveals evolutionarily conserved genetic mechanisms forvertebrate head specification. Development. 2004 Jan;131(1):57-71. doi:10.1242/dev.00877. Epub 2003 Nov 26. PMID: 14645121.

48. Korzh V. Development of brain ventricular system. Cell Mol Life Sci. 2018Feb;75(3):375-383. doi: 10.1007/s00018-017-2605-y. Epub 2017 Aug 5. PMID:28780589; PMCID: PMC5765195.

49. Kroenke CD, Bayly PV. How Forces Fold the Cerebral Cortex. J Neurosci. 2018Jan 24;38(4):767-775. doi: 10.1523/JNEUROSCI.1105-17.2017. PMID:29367287; PMCID: PMC5783962.

50. Kwon GS, Hadjantonakis AK. Transthyretin mouse transgenes direct RFPexpression or Cre-mediated recombination throughout the visceral endoderm.Genesis. 2009 Jul;47(7):447-55. doi: 10.1002/dvg.20522. PMID: 19415627;PMCID: PMC2878311.

51. Lehtinen MK, Zappaterra MW, Chen X, Yang YJ, Hill AD, Lun M, Maynard T,Gonzalez D, Kim S, Ye P, D'Ercole AJ, Wong ET, LaMantia AS, Walsh CA. Thecerebrospinal fluid provides a proliferative niche for neural progenitor cells.Neuron. 2011 Mar 10;69(5):893-905. doi: 10.1016/j.neuron.2011.01.023. PMID:21382550; PMCID: PMC3085909.

52. Lehtinen MK, Bjornsson CS, Dymecki SM, Gilbertson RJ, Holtzman DM,Monuki ES. The choroid plexus and cerebrospinal fluid: emerging roles indevelopment, disease, and therapy. J Neurosci. 2013 Nov 6;33(45):17553-9. doi:10.1523/JNEUROSCI.3258-13.2013. PMID: 24198345; PMCID: PMC3818536.(a)

53. Lehtinen MK, Zappaterra MW, Chen X, Yang YJ, Hill AD, Lun M, Maynard T,Gonzalez D, Kim S, Ye P, D'Ercole AJ, Wong ET, LaMantia AS, Walsh CA. Thecerebrospinal fluid provides a proliferative niche for neural progenitor cells.Neuron. 2011 Mar 10;69(5):893-905. doi: 10.1016/j.neuron.2011.01.023. PMID:21382550; PMCID: PMC3085909.(b)

54. Li L, Grausam KB, Wang J, Lun MP, Ohli J, Lidov HG, Calicchio ML, Zeng E,Salisbury JL, Wechsler-Reya RJ, Lehtinen MK, Schüller U, Zhao H. SonicHedgehog promotes proliferation of Notch-dependent monociliated choroidplexus tumour cells. Nat Cell Biol. 2016 Apr;18(4):418-30. doi: 10.1038/ncb3327.Epub 2016 Mar 21. PMID: 26999738; PMCID: PMC4814324.

55. Lois C, Alvarez-Buylla A. Long-distance neuronal migration in the adultmammalian brain. Science. 1994 May 20;264(5162):1145-8. doi:10.1126/science.8178174. PMID: 8178174.

56. Lun MP, Monuki ES, Lehtinen MK. Development and functions of the choroidplexus-cerebrospinal fluid system. Nat Rev Neurosci. 2015 Aug;16(8):445-57.doi: 10.1038/nrn3921. Epub 2015 Jul 15. PMID: 26174708; PMCID:PMC4629451.(a)

57. Lun MP, Johnson MB, Broadbelt KG, Watanabe M, Kang YJ, Chau KF, SpringelMW, Malesz A, Sousa AM, Pletikos M, Adelita T, Calicchio ML, Zhang Y,Holtzman MJ, Lidov HG, Sestan N, Steen H, Monuki ES, Lehtinen MK.Spatially heterogeneous choroid plexus transcriptomes encode positionalidentity and contribute to regional CSF production. J Neurosci. 2015 Mar25;35(12):4903-16. doi: 10.1523/JNEUROSCI.3081-14.2015. Erratum in: JNeurosci. 2015 Jun 3;35(22):8686. Adelita, Tai [corrected to Adelita, Tais].PMID: 25810521; PMCID: PMC4389594.(b)

58. Mallamaci A, Di Blas E, Briata P, Boncinelli E, Corte G. OTX2 homeoprotein inthe developing central nervous system and migratory cells of the olfactory area.Mech Dev. 1996 Aug;58(1-2):165-78. doi: 10.1016/s0925-4773(96)00571-0.PMID: 8887325.

59. Memi F, Zecevic N, Radonjić N. Multiple roles of Sonic Hedgehog in thedeveloping human cortex are suggested by its widespread distribution. BrainStruct Funct. 2018 Jun;223(5):2361-2375. doi: 10.1007/s00429-018-1621-5.Epub 2018 Feb 28. PMID: 29492654; PMCID: PMC5968052.

60. Miller FD, Gauthier AS. Timing is everything: making neurons versus glia inthe developing cortex. Neuron. 2007 May 3;54(3):357-69. doi:10.1016/j.neuron.2007.04.019. PMID: 17481390.

61. Mirzaa G, Parry DA, Fry AE, Giamanco KA, Schwartzentruber J, Vanstone M,Logan CV, Roberts N, Johnson CA, Singh S, Kholmanskikh SS, Adams C,Hodge RD, Hevner RF, Bonthron DT, Braun KPJ, Faivre L, Rivière JB, St-OngeJ, Gripp KW, Mancini GM, Pang K, Sweeney E, van Esch H, Verbeek N,Wieczorek D, Steinraths M, Majewski J; FORGE Canada Consortium, BoycotKM, Pilz DT, Ross ME, Dobyns WB, Sheridan EG. De novo CCND2 mutationsleading to stabilization of cyclin D2 cause.megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. NatGenet. 2014 May;46(5):510-515. doi: 10.1038/ng.2948. Epub 2014 Apr 6. PMID:24705253; PMCID: PMC4004933

62. Myung J, Schmal C, Hong S, Tsukizawa Y, Rose P, Zhang Y, Holtzman MJ, DeSchutter E, Herzel H, Bordyugov G, Takumi T. The choroid plexus is animportant circadian clock component. Nat Commun. 2018 Mar 14;9(1):1062.doi: 10.1038/s41467-018-03507-2. Erratum in: Nat Commun. 2019 Nov20;10(1):5253. PMID: 29540683; PMCID: PMC5852131.

63. Nagata Y, Tashiro F, Yi S, Murakami T, Maeda S, Takahashi K, Shimada K,Okamura H, Yamamura K. A 6-kb upstream region of the human transthyretingene can direct developmental, tissue-specific, and quantitatively normalexpression in transgenic mouse. J Biochem. 1995 Jan;117(1):169-75. doi:10.1093/oxfordjournals.jbchem.a124705. PMID: 7775385.

64. Nielsen CM, Dymecki SM. Sonic hedgehog is required for vascular outgrowth inthe hindbrain choroid plexus. Dev Biol. 2010 Apr 15;340(2):430-7. doi:10.1016/j.ydbio.2010.01.032. Epub 2010 Feb 1. PMID: 20123094; PMCID:PMC2897143.

65. Noctor SC, Flint AC, Weissman TA, Dammerman RS, Kriegstein AR. Neuronsderived from radial glial cells establish radial units in neocortex. Nature. 2001Feb 8;409(6821):714-20. doi: 10.1038/35055553. PMID: 11217860.

66. Nonaka-Kinoshita M, Reillo I, Artegiani B, Martínez-Martínez MÁ, Nelson M,Borrell V, Calegari F. Regulation of cerebral cortex size and folding byexpansion of basal progenitors. EMBO J. 2013 Jul 3;32(13):1817-28. doi:10.1038/emboj.2013.96. Epub 2013 Apr 26. PMID: 23624932; PMCID:PMC3926188.

67. Ohtsuka T, Kageyama R. Hes1 overexpression leads to expansion of embryonicneural stem cell pool and stem cell reservoir in the postnatal brain.Development. 2021 Feb 17;148(4):dev189191. doi: 10.1242/dev.189191. PMID:33531431. (a)

68. Ohtsuka T, Kageyama R. Dual activation of Shh and Notch signaling inducesdramatic enlargement of neocortical surface area. Neurosci Res. 2021 Sep30:S0168-0102(21)00208-X. doi: 10.1016/j.neures.2021.09.006. Epub ahead ofprint. PMID: 34600946. (b)

69. Park MG, Jang H, Lee SH, Lee CJ. Flow Shear Stress Enhances theProliferative Potential of Cultured Radial Glial Cells Possibly Via an Activationof Mechanosensitive Calcium Channel. Exp Neurobiol. 2017 Apr;26(2):71-81.doi: 10.5607/en.2017.26.2.71. Epub 2017 Apr 13. PMID: 28442943; PMCID:PMC5403909.

70. Planques A, Oliveira Moreira V, Dubreuil C, Prochiantz A, Di Nardo AA. OTX2Signals from the Choroid Plexus to Regulate Adult Neurogenesis. eNeuro. 2019May 7;6(2):ENEURO.0262-18.2019. doi: 10.1523/ENEURO.0262-18.2019.PMID: 31064838; PMCID: PMC6506823.

71. Regev L, Ezrielev E, Gershon E, Gil S, Chen A. Genetic approach forintracerebroventricular delivery. Proc Natl Acad Sci U S A. 2010 Mar2;107(9):4424-9. doi: 10.1073/pnas.0907059107. Epub 2010 Feb 8. PMID:20142482; PMCID: PMC2840118.

72. Rakic P. A small step for the cell, a giant leap for mankind: a hypothesis ofneocortical expansion during evolution. Trends Neurosci. 1995 Sep;18(9):383-8.doi: 10.1016/0166-2236(95)93934-p. PMID: 7482803.

73. Reillo I, de Juan Romero C, García-Cabezas MÁ, Borrell V. A role forintermediate radial glia in the tangential expansion of the mammalian cerebralcortex. Cereb Cortex. 2011 Jul;21(7):1674-94. doi: 10.1093/cercor/bhq238. Epub2010 Dec 2. PMID: 21127018.

74. Sakamoto M, Ieki N, Miyoshi G, Mochimaru D, Miyachi H, Imura T, YamaguchiM, Fishell G, Mori K, Kageyama R, Imayoshi I. Continuous postnatalneurogenesis contributes to formation of the olfactory bulb neural circuits andflexible olfactory associative learning. J Neurosci. 2014 Apr 23;34(17):5788-99.doi: 10.1523/JNEUROSCI.0674-14.2014. PMID: 24760839; PMCID:PMC6608281.

75. Saunders NR, Daneman R, Dziegielewska KM, Liddelow SA. Transporters ofthe blood-brain and blood-CSF interfaces in development and in the adult. MolAspects Med. 2013 Apr-Jun;34(2-3):742-52. doi: 10.1016/j.mam.2012.11.006.PMID: 23506907.

76. Saunders NR, Dziegielewska KM, Møllgård K, Habgood MD, Wakefield MJ,Lindsay H, Stratzielle N, Ghersi-Egea JF, Liddelow SA. Influx mechanisms inthe embryonic and adult rat choroid plexus: a transcriptome study. FrontNeurosci. 2015 Apr 28;9:123. doi: 10.3389/fnins.2015.00123. PMID: 25972776;PMCID: PMC4412010

77. Shinmyo Y, Terashita Y, Dinh Duong TA, Horiike T, Kawasumi M, Hosomichi K,Tajima A, Kawasaki H. Folding of the Cerebral Cortex Requires Cdk5 inUpper-Layer Neurons in Gyrencephalic Mammals. Cell Rep. 2017 Aug29;20(9):2131-2143. doi: 10.1016/j.celrep.2017.08.024. PMID: 28854363.

78. Shqirat M, Kinoshita A, Kageyama R, Ohtsuka T. Sonic hedgehog expandsneural stem cells in the neocortical region leading to an expanded and wrinkledneocortical surface. Genes Cells. 2021 Jun;26(6):399-410. doi: 10.1111/gtc.12847.Epub 2021 Apr 14. PMID: 33811429.

79. Shiraishi N, Nakashima T, Yamada S, Uwabe C, Kose K, Takakuwa T.Morphogenesis of lateral choroid plexus during human embryonic period. AnatRec (Hoboken). 2013 Apr;296(4):692-700. doi: 10.1002/ar.22662. Epub 2013 Feb9. PMID: 23401483.

80. Silva-Vargas V, Maldonado-Soto AR, Mizrak D, Codega P, Doetsch F.Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult NeuralStem Cells. Cell Stem Cell. 2016 Nov 3;19(5):643-652. doi:10.1016/j.stem.2016.06.013. Epub 2016 Jul 21. PMID: 27452173

81. Smart IH, Dehay C, Giroud P, Berland M, Kennedy H. Unique morphologicalfeatures of the proliferative zones and postmitotic compartments of the neuralepithelium giving rise to striate and extrastriate cortex in the monkey. CerebCortex. 2002 Jan;12(1):37-53. doi: 10.1093/cercor/12.1.37. PMID: 11734531;PMCID: PMC1931430.

82. Stahl R, Walcher T, De Juan Romero C, Pilz GA, Cappello S, Irmler M,Sanz-Aquela JM, Beckers J, Blum R, Borrell V, Götz M. Trnp1 regulatesexpansion and folding of the mammalian cerebral cortex by control of radialglial fate. Cell. 2013 Apr 25;153(3):535-49. doi: 10.1016/j.cell.2013.03.027.PMID: 23622239.

83. Stopa EG, Tanis KQ, Miller MC, Nikonova EV, Podtelezhnikov AA, Finney EM,Stone DJ, Camargo LM, Parker L, Verma A, Baird A, Donahue JE, Torabi T,Eliceiri BP, Silverberg GD, Johanson CE. Comparative transcriptomics ofchoroid plexus in Alzheimer's disease, frontotemporal dementia andHuntington's disease: implications for CSF homeostasis. Fluids Barriers CNS.2018 May 31;15(1):18. doi: 10.1186/s12987-018-0102-9. PMID: 29848382;PMCID: PMC5977762.

84. Susaki EA, Tainaka K, Perrin D, Yukinaga H, Kuno A, Ueda HR. AdvancedCUBIC protocols for whole-brain and whole-body clearing and imaging. NatProtoc. 2015 Nov;10(11):1709-27. doi: 10.1038/nprot.2015.085. Epub 2015 Oct 8.PMID: 26448360.

85. Suzuki IK, Gacquer D, Van Heurck R, Kumar D, Wojno M, Bilheu A, Herpoel A,Lambert N, Cheron J, Polleux F, Detours V, Vanderhaeghen P. Human-SpecificNOTCH2NL Genes Expand Cortical Neurogenesis through Delta/NotchRegulation. Cell. 2018 May 31;173(6):1370-1384.e16. doi:10.1016/j.cell.2018.03.067. Epub 2018 May 31. PMID: 29856955; PMCID:PMC6092419.

86. Thouvenot E, Lafon-Cazal M, Demettre E, Jouin P, Bockaert J, Marin P. Theproteomic analysis of mouse choroid plexus secretome reveals a high proteinsecretion capacity of choroidal epithelial cells. Proteomics. 2006Nov;6(22):5941-52. doi: 10.1002/pmic.200600096. PMID: 17051638.

87. Tsunekawa Y, Britto JM, Takahashi M, Polleux F, Tan SS, Osumi N. Cyclin D2in the basal process of neural progenitors is linked to non-equivalent cell fates.EMBO J. 2012 Apr 18;31(8):1879-92. doi: 10.1038/emboj.2012.43. Epub 2012Mar 6. PMID: 22395070; PMCID: PMC3343330.

88. Tsunekawa Y, Kikkawa T, Osumi N. Asymmetric inheritance of Cyclin D2maintains proliferative neural stem/progenitor cells: a critical event in braindevelopment and evolution. Dev Growth Differ. 2014 Jun;56(5):349-57. doi:10.1111/dgd.12135. Epub 2014 May 17. PMID: 24835888.

89. Van Essen DC, Donahue CJ, Coalson TS, Kennedy H, Hayashi T, Glasser MF.Cerebral cortical folding, parcellation, and connectivity in humans, nonhumanprimates, and mice. Proc Natl Acad Sci U S A. 2019 Dec 23;116(52):26173–80.doi: 10.1073/pnas.1902299116. Epub ahead of print. PMID: 31871175; PMCID:PMC6936571.

90. Wang L, Hou S, Han YG. Hedgehog signaling promotes basal progenitorexpansion and the growth and folding of the neocortex. Nat Neurosci. 2016Jul;19(7):888-96. doi: 10.1038/nn.4307. Epub 2016 May 23. PMID: 27214567;PMCID: PMC4925239.

91. Winkler CC, Yabut OR, Fregoso SP, Gomez HG, Dwyer BE, Pleasure SJ, FrancoSJ. The Dorsal Wave of Neocortical Oligodendrogenesis Begins Embryonicallyand Requires Multiple Sources of Sonic Hedgehog. J Neurosci. 2018 Jun6;38(23):5237-5250. doi: 10.1523/JNEUROSCI.3392-17.2018. Epub 2018 May 8.PMID: 29739868; PMCID: PMC5990977.

92. Wong FK, Fei JF, Mora-Bermúdez F, Taverna E, Haffner C, Fu J, AnastassiadisK, Stewart AF, Huttner WB. Sustained Pax6 Expression GeneratesPrimate-like Basal Radial Glia in Developing Mouse Neocortex. PLoS Biol.2015 Aug 7;13(8):e1002217. doi: 10.1371/journal.pbio.1002217. PMID:26252244; PMCID: PMC4529158.

93. Xu G, Knutsen AK, Dikranian K, Kroenke CD, Bayly PV, Taber LA. Axons pullon the brain, but tension does not drive cortical folding. J Biomech Eng. 2010Jul;132(7):071013. doi: 10.1115/1.4001683. PMID: 20590291; PMCID:PMC3170872.

94. Yan C, Costa RH, Darnell JE Jr, Chen JD, Van Dyke TA. Distinct positive andnegative elements control the limited hepatocyte and choroid plexus expressionof transthyretin in transgenic mice. EMBO J. 1990 Mar;9(3):869-78. PMID:1690125; PMCID: PMC551747.

95. Zappaterra MD, Lisgo SN, Lindsay S, Gygi SP, Walsh CA, Ballif BA. Acomparative proteomic analysis of human and rat embryonic cerebrospinal fluid.J Proteome Res. 2007 Sep;6(9):3537-48. doi: 10.1021/pr070247w. Epub 2007Aug 16. PMID: 17696520.

96. Zappaterra MW, Lehtinen MK. The cerebrospinal fluid: regulator ofneurogenesis, behavior, and beyond. Cell Mol Life Sci. 2012 Sep;69(17):2863-78.doi: 10.1007/s00018-012-0957-x. Epub 2012 Mar 14. PMID: 22415326; PMCID:PMC3856656.

参考文献をもっと見る