Deconstructing cerebellar development cell by cell
Autoři:
Max J. van Essen aff001; Samuel Nayler aff001; Esther B. E. Becker aff001; John Jacob aff002
Působiště autorů:
Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
aff001; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
aff002
Vyšlo v časopise:
Deconstructing cerebellar development cell by cell. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008630
Kategorie:
Review
doi:
https://doi.org/10.1371/journal.pgen.1008630
Souhrn
The cerebellum is a pivotal centre for the integration and processing of motor and sensory information. Its extended development into the postnatal period makes this structure vulnerable to a variety of pathologies, including neoplasia. These properties have prompted intensive investigations that reveal not only developmental mechanisms in common with other regions of the neuraxis but also unique strategies to generate neuronal diversity. How the phenotypically distinct cell types of the cerebellum emerge rests on understanding how gene expression differences arise in a spatially and temporally coordinated manner from initially homogeneous cell populations. Increasingly sophisticated fate mapping approaches, culminating in genetic-induced fate mapping, have furthered the understanding of lineage relationships between early- versus later-born cells. Tracing the developmental histories of cells in this way coupled with analysis of gene expression patterns has provided insight into the developmental genetic programmes that instruct cellular heterogeneity. A limitation to date has been the bulk analysis of cells, which blurs lineage relationships and obscures gene expression differences between cells that underpin the cellular taxonomy of the cerebellum. This review emphasises recent discoveries, focusing mainly on single-cell sequencing in mouse and parallel human studies that elucidate neural progenitor developmental trajectories with unprecedented resolution. Complementary functional studies of neural repair after cerebellar injury are challenging assumptions about the stability of postnatal cellular identities. The result is a wealth of new information about the developmental mechanisms that generate cerebellar neural diversity, with implications for human evolution.
Klíčová slova:
Cerebellum – Gene expression – Granule cells – Homeobox – Interneurons – Neurons – Purkinje cells – Transcription factors
Zdroje
1. Bruchhage MMK, Bucci MP, Becker EBE. Cerebellar involvement in autism and ADHD. Handb Clin Neurol. 2018;155:61–72. doi: 10.1016/B978-0-444-64189-2.00004-4 29891077.
2. Sathyanesan A, Zhou J, Scafidi J, Heck DH, Sillitoe RV, Gallo V. Emerging connections between cerebellar development, behaviour and complex brain disorders. Nat Rev Neurosci. 2019;20(5):298–313. doi: 10.1038/s41583-019-0152-2 30923348.
3. Rakic P, Sidman RL. Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans. J Comp Neurol. 1970;139(4):473–500. doi: 10.1002/cne.901390407 4195699.
4. Haldipur P, Bharti U, Alberti C, Sarkar C, Gulati G, Iyengar S, et al. Preterm delivery disrupts the developmental program of the cerebellum. PLoS ONE. 2011;6(8):e23449. doi: 10.1371/journal.pone.0023449 21858122; PubMed Central PMCID: PMC3157376.
5. Yachnis AT, Rorke LB. Cerebellar and brainstem development: an overview in relation to Joubert syndrome. J Child Neurol. 1999;14(9):570–3. doi: 10.1177/088307389901400904 10488901.
6. Trivedi R, Gupta RK, Husain N, Rathore RK, Saksena S, Srivastava S, et al. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology. Neuroradiology. 2009;51(9):567–76. doi: 10.1007/s00234-009-0533-8 19421746.
7. Haldipur P, Dang D, Millen KJ. Embryology. Handb Clin Neurol. 2018;154:29–44. doi: 10.1016/B978-0-444-63956-1.00002-3 29903446; PubMed Central PMCID: PMC6231496.
8. Sillitoe RV, Joyner AL. Morphology, molecular codes, and circuitry produce the three-dimensional complexity of the cerebellum. Annu Rev Cell Dev Biol. 2007;23:549–77. doi: 10.1146/annurev.cellbio.23.090506.123237 17506688.
9. Leto K, Arancillo M, Becker EB, Buffo A, Chiang C, Ding B, et al. Consensus Paper: Cerebellar Development. Cerebellum. 2016;15(6):789–828. doi: 10.1007/s12311-015-0724-2 26439486; PubMed Central PMCID: PMC4846577.
10. Millet S, Bloch-Gallego E, Simeone A, Alvarado-Mallart RM. The caudal limit of Otx2 gene expression as a marker of the midbrain/hindbrain boundary: a study using in situ hybridisation and chick/quail homotopic grafts. Development. 1996;122(12):3785–97. 9012500.
11. Wingate RJ, Hatten ME. The role of the rhombic lip in avian cerebellum development. Development. 1999;126(20):4395–404. 10498676.
12. Martinez Arias A, Steventon B. On the nature and function of organizers. Development. 2018;145(5). doi: 10.1242/dev.159525 29523654; PubMed Central PMCID: PMC5868996.
13. Sunmonu NA, Li K, Guo Q, Li JY. Gbx2 and Fgf8 are sequentially required for formation of the midbrain-hindbrain compartment boundary. Development. 2011;138(4):725–34. doi: 10.1242/dev.055665 21266408; PubMed Central PMCID: PMC3026416.
14. Cheng FY, Huang X, Sarangi A, Ketova T, Cooper MK, Litingtung Y, et al. Widespread contribution of Gdf7 lineage to cerebellar cell types and implications for hedgehog-driven medulloblastoma formation. PLoS ONE. 2012;7(4):e35541. doi: 10.1371/journal.pone.0035541 22539980; PubMed Central PMCID: PMC3335071.
15. Lee KJ, Jessell TM. The specification of dorsal cell fates in the vertebrate central nervous system. Annu Rev Neurosci. 1999;22:261–94. doi: 10.1146/annurev.neuro.22.1.261 10202540.
16. Chizhikov VV, Lindgren AG, Currle DS, Rose MF, Monuki ES, Millen KJ. The roof plate regulates cerebellar cell-type specification and proliferation. Development. 2006;133(15):2793–804. doi: 10.1242/dev.02441 16790481.
17. Davidson BP, Tam PP. The node of the mouse embryo. Curr Biol. 2000;10(17):R617–9. doi: 10.1016/s0960-9822(00)00675-8 10996084.
18. Bujakowska KM, Liu Q, Pierce EA. Photoreceptor Cilia and Retinal Ciliopathies. Cold Spring Harb Perspect Biol. 2017;9(10). doi: 10.1101/cshperspect.a028274 28289063; PubMed Central PMCID: PMC5629997.
19. Louie CM, Gleeson JG. Genetic basis of Joubert syndrome and related disorders of cerebellar development. Hum Mol Genet. 2005;14 Spec No. 2:R235–42. doi: 10.1093/hmg/ddi264 16244321.
20. Goetz SC, Anderson KV. The primary cilium: a signalling centre during vertebrate development. Nat Rev Genet. 2010;11(5):331–44. doi: 10.1038/nrg2774 PubMed Central PMCID: PMC3121168. 20395968
21. Lancaster MA, Gopal DJ, Kim J, Saleem SN, Silhavy JL, Louie CM, et al. Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome. Nat Med. 2011;17(6):726–31. doi: 10.1038/nm.2380 21623382; PubMed Central PMCID: PMC3110639.
22. Griffiths JA, Scialdone A, Marioni JC. Using single-cell genomics to understand developmental processes and cell fate decisions. Mol Syst Biol. 2018;14(4):e8046. doi: 10.15252/msb.20178046 PubMed Central PMCID: PMC5900446. 29661792
23. Wizeman JW, Guo Q, Wilion EM, Li JY. Specification of diverse cell types during early neurogenesis of the mouse cerebellum. Elife. 2019;8. doi: 10.7554/eLife.42388 30735127; PubMed Central PMCID: PMC6382353.
24. Dodd J, Jessell TM, Placzek M. The when and where of floor plate induction. Science. 1998;282(5394):1654–7. doi: 10.1126/science.282.5394.1654 9867664.
25. Alexandre P, Wassef M. The isthmic organizer links anteroposterior and dorsoventral patterning in the mid/hindbrain by generating roof plate structures. Development. 2003;130(22):5331–8. doi: 10.1242/dev.00756 14507781.
26. Louvi A, Alexandre P, Metin C, Wurst W, Wassef M. The isthmic neuroepithelium is essential for cerebellar midline fusion. Development. 2003;130(22):5319–30. doi: 10.1242/dev.00736 14507778.
27. Xu J, Liu Z, Ornitz DM. Temporal and spatial gradients of Fgf8 and Fgf17 regulate proliferation and differentiation of midline cerebellar structures. Development. 2000;127(9):1833–43. 10751172.
28. Yu T, Meiners LC, Danielsen K, Wong MT, Bowler T, Reinberg D, et al. Deregulated FGF and homeotic gene expression underlies cerebellar vermis hypoplasia in CHARGE syndrome. Elife. 2013;2:e01305. doi: 10.7554/eLife.01305 24368733; PubMed Central PMCID: PMC3870572.
29. Zanni G, Barresi S, Travaglini L, Bernardini L, Rizza T, Digilio MC, et al. FGF17, a gene involved in cerebellar development, is downregulated in a patient with Dandy-Walker malformation carrying a de novo 8p deletion. Neurogenetics. 2011;12(3):241–5. doi: 10.1007/s10048-011-0283-8 21484435.
30. Lancioni A, Pizzo M, Fontanella B, Ferrentino R, Napolitano LM, De Leonibus E, et al. Lack of Mid1, the mouse ortholog of the Opitz syndrome gene, causes abnormal development of the anterior cerebellar vermis. J Neurosci. 2010;30(8):2880–7. doi: 10.1523/JNEUROSCI.4196-09.2010 20181585; PubMed Central PMCID: PMC6633954.
31. Haldipur P. Spatiotemporal expansion of primary progenitor zones in the developing human cerebellum. Science. 2019; doi: 10.1126/science.aax7526 31624095
32. Basson MA, Wingate RJ. Congenital hypoplasia of the cerebellum: developmental causes and behavioral consequences. Front Neuroanat. 2013;7:29. doi: 10.3389/fnana.2013.00029 24027500; PubMed Central PMCID: PMC3759752.
33. Huang X, Liu J, Ketova T, Fleming JT, Grover VK, Cooper MK, et al. Transventricular delivery of Sonic hedgehog is essential to cerebellar ventricular zone development. Proc Natl Acad Sci U S A. 2010;107(18):8422–7. doi: 10.1073/pnas.0911838107 20400693; PubMed Central PMCID: PMC2889567.
34. Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura YV, et al. Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. Neuron. 2005;47(2):201–13. doi: 10.1016/j.neuron.2005.06.007 16039563.
35. Pascual M, Abasolo I, Mingorance-Le Meur A, Martinez A, Del Rio JA, Wright CV, et al. Cerebellar GABAergic progenitors adopt an external granule cell-like phenotype in the absence of Ptf1a transcription factor expression. Proc Natl Acad Sci U S A. 2007;104(12):5193–8. doi: 10.1073/pnas.0605699104 17360405; PubMed Central PMCID: PMC1829285.
36. Carter RA, Bihannic L, Rosencrance C, Hadley JL, Tong Y, Phoenix TN, et al. A Single-Cell Transcriptional Atlas of the Developing Murine Cerebellum. Curr Biol. 2018;28(18):2910–20 e2. doi: 10.1016/j.cub.2018.07.062 30220501.
37. Blondel VD, Guillaume J, Lamboitte R, Lefebvre E. Fast unfolding of communities in large networks. Journal of Statistical Mechanics: Theory and Experiment. 2008;(10):10008.
38. Jacob J, Maurange C, Gould AP. Temporal control of neuronal diversity: common regulatory principles in insects and vertebrates? Development. 2008;135(21):3481–9. doi: 10.1242/dev.016931 18849528.
39. Seto Y, Nakatani T, Masuyama N, Taya S, Kumai M, Minaki Y, et al. Temporal identity transition from Purkinje cell progenitors to GABAergic interneuron progenitors in the cerebellum. Nat Commun. 2014;5:3337. doi: 10.1038/ncomms4337 24535035; PubMed Central PMCID: PMC5669625.
40. Zordan P, Croci L, Hawkes R, Consalez GG. Comparative analysis of proneural gene expression in the embryonic cerebellum. Dev Dyn. 2008;237(6):1726–35. doi: 10.1002/dvdy.21571 18498101.
41. Tritschler S, Buttner M, Fischer DS, Lange M, Bergen V, Lickert H, et al. Concepts and limitations for learning developmental trajectories from single cell genomics. Development. 2019;146(12). doi: 10.1242/dev.170506 31249007.
42. Altman J, Bayer SA. Development of the Cerebellar System: In Relation to Its Evolution, Structure, and Functions. Boca Raton: CRC Press; 1997.
43. Dastjerdi FV, Consalez GG, Hawkes R. Pattern formation during development of the embryonic cerebellum. Front Neuroanat. 2012;6:10. doi: 10.3389/fnana.2012.00010 22493569; PubMed Central PMCID: PMC3318227.
44. Hashimoto M, Mikoshiba K. Mediolateral compartmentalization of the cerebellum is determined on the "birth date" of Purkinje cells. J Neurosci. 2003;23(36):11342–51. doi: 10.1523/JNEUROSCI.23-36-11342.2003 14672998.
45. Fujita H, Morita N, Furuichi T, Sugihara I. Clustered fine compartmentalization of the mouse embryonic cerebellar cortex and its rearrangement into the postnatal striped configuration. J Neurosci. 2012;32(45):15688–703. doi: 10.1523/JNEUROSCI.1710-12.2012 23136409.
46. Sugihara I, Fujita H. Peri- and postnatal development of cerebellar compartments in the mouse. Cerebellum. 2013;12(3):325–7. doi: 10.1007/s12311-013-0450-6 23335119.
47. Xu X, Stoyanova EI, Lemiesz AE, Xing J, Mash DC, Heintz N. Species and cell-type properties of classically defined human and rodent neurons and glia. Elife. 2018;7. doi: 10.7554/eLife.37551 30320555; PubMed Central PMCID: PMC6188473.
48. Leto K, Bartolini A, Rossi F. The prospective white matter: an atypical neurogenic niche in the developing cerebellum. Arch Ital Biol. 2010;148(2):137–46. 20830975.
49. Machold R, Fishell G. Math1 is expressed in temporally discrete pools of cerebellar rhombic-lip neural progenitors. Neuron. 2005;48(1):17–24. doi: 10.1016/j.neuron.2005.08.028 16202705.
50. Englund C, Kowalczyk T, Daza RA, Dagan A, Lau C, Rose MF, et al. Unipolar brush cells of the cerebellum are produced in the rhombic lip and migrate through developing white matter. J Neurosci. 2006;26(36):9184–95. doi: 10.1523/JNEUROSCI.1610-06.2006 16957075.
51. Chizhikov VV, Lindgren AG, Mishima Y, Roberts RW, Aldinger KA, Miesegaes GR, et al. Lmx1a regulates fates and location of cells originating from the cerebellar rhombic lip and telencephalic cortical hem. Proc Natl Acad Sci U S A. 2010;107(23):10725–30. doi: 10.1073/pnas.0910786107 20498066; PubMed Central PMCID: PMC2890798.
52. Yeung J, Ha TJ, Swanson DJ, Choi K, Tong Y, Goldowitz D. Wls provides a new compartmental view of the rhombic lip in mouse cerebellar development. J Neurosci. 2014;34(37):12527–37. doi: 10.1523/JNEUROSCI.1330-14.2014 25209290; PubMed Central PMCID: PMC4160781.
53. Legue E, Riedel E, Joyner AL. Clonal analysis reveals granule cell behaviors and compartmentalization that determine the folded morphology of the cerebellum. Development. 2015;142(9):1661–71. doi: 10.1242/dev.120287 25834018; PubMed Central PMCID: PMC4419279.
54. Millen KJ, Hui CC, Joyner AL. A role for En-2 and other murine homologues of Drosophila segment polarity genes in regulating positional information in the developing cerebellum. Development. 1995;121(12):3935–45. 8575294.
55. Karam SD, Burrows RC, Logan C, Koblar S, Pasquale EB, Bothwell M. Eph receptors and ephrins in the developing chick cerebellum: relationship to sagittal patterning and granule cell migration. J Neurosci. 2000;20(17):6488–500. doi: 10.1523/JNEUROSCI.20-17-06488.2000 10964955.
56. Blaess S, Graus-Porta D, Belvindrah R, Radakovits R, Pons S, Littlewood-Evans A, et al. Beta1-integrins are critical for cerebellar granule cell precursor proliferation. J Neurosci. 2004;24(13):3402–12. doi: 10.1523/JNEUROSCI.5241-03.2004 15056720; PubMed Central PMCID: PMC2693074.
57. Mishra R, Gupta SK, Meiri KF, Fong M, Thostrup P, Juncker D, et al. GAP-43 is key to mitotic spindle control and centrosome-based polarization in neurons. Cell Cycle. 2008;7(3):348–57. doi: 10.4161/cc.7.3.5235 18235238.
58. Wechsler-Reya R, Scott MP. The developmental biology of brain tumors. Annu Rev Neurosci. 2001;24:385–428. doi: 10.1146/annurev.neuro.24.1.385 11283316.
59. Ben-Arie N, Bellen HJ, Armstrong DL, McCall AE, Gordadze PR, Guo Q, et al. Math1 is essential for genesis of cerebellar granule neurons. Nature. 1997;390(6656):169–72. doi: 10.1038/36579 9367153.
60. Forget A, Bihannic L, Cigna SM, Lefevre C, Remke M, Barnat M, et al. Shh signaling protects Atoh1 from degradation mediated by the E3 ubiquitin ligase Huwe1 in neural precursors. Dev Cell. 2014;29(6):649–61. doi: 10.1016/j.devcel.2014.05.014 24960692.
61. Chang CH, Zanini M, Shirvani H, Cheng JS, Yu H, Feng CH, et al. Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation. Dev Cell. 2019;48(2):184–99 e5. doi: 10.1016/j.devcel.2018.12.017 30695697.
62. Johnston RJ Jr., Desplan C. Stochastic mechanisms of cell fate specification that yield random or robust outcomes. Annu Rev Cell Dev Biol. 2010;26:689–719. doi: 10.1146/annurev-cellbio-100109-104113 20590453; PubMed Central PMCID: PMC3025287.
63. Vladoiu MC, El-Hamamy I, Donovan LK, Farooq H, Holgado BL, Sundaravadanam Y, et al. Childhood cerebellar tumours mirror conserved fetal transcriptional programs. Nature. 2019;572(7767):67–73. doi: 10.1038/s41586-019-1158-7 31043743; PubMed Central PMCID: PMC6675628.
64. Stauber M, Weidemann M, Dittrich-Breiholz O, Lobschat K, Alten L, Mai M, et al. Identification of FOXJ1 effectors during ciliogenesis in the foetal respiratory epithelium and embryonic left-right organiser of the mouse. Dev Biol. 2017;423(2):170–88. doi: 10.1016/j.ydbio.2016.11.019 27914912.
65. Onoufriadis A, Shoemark A, Schmidts M, Patel M, Jimenez G, Liu H, et al. Targeted NGS gene panel identifies mutations in RSPH1 causing primary ciliary dyskinesia and a common mechanism for ciliary central pair agenesis due to radial spoke defects. Hum Mol Genet. 2014;23(13):3362–74. doi: 10.1093/hmg/ddu046 24518672; PubMed Central PMCID: PMC4049301.
66. Thompson CL, Ng L, Menon V, Martinez S, Lee CK, Glattfelder K, et al. A high-resolution spatiotemporal atlas of gene expression of the developing mouse brain. Neuron. 2014;83(2):309–23. doi: 10.1016/j.neuron.2014.05.033 24952961; PubMed Central PMCID: PMC4319559.
67. Wojcinski A, Lawton AK, Bayin NS, Lao Z, Stephen DN, Joyner AL. Cerebellar granule cell replenishment postinjury by adaptive reprogramming of Nestin(+) progenitors. Nat Neurosci. 2017;20(10):1361–70. doi: 10.1038/nn.4621 28805814; PubMed Central PMCID: PMC5614835.
68. Jacob J, Briscoe J. Gli proteins and the control of spinal-cord patterning. EMBO Rep. 2003;4(8):761–5. doi: 10.1038/sj.embor.embor896 12897799; PubMed Central PMCID: PMC1326336.
69. Dessaud E, McMahon AP, Briscoe J. Pattern formation in the vertebrate neural tube: a sonic hedgehog morphogen-regulated transcriptional network. Development. 2008;135(15):2489–503. doi: 10.1242/dev.009324 18621990.
70. Bayin NS, Wojcinski A, Mourton A, Saito H, Suzuki N, Joyner AL. Age-dependent dormant resident progenitors are stimulated by injury to regenerate Purkinje neurons. Elife. 2018;7. doi: 10.7554/eLife.39879 30091706; PubMed Central PMCID: PMC6115187.
71. Lake BB, Chen S, Sos BC, Fan J, Kaeser GE, Yung YC, et al. Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain. Nat Biotechnol. 2018;36(1):70–80. doi: 10.1038/nbt.4038 29227469.
72. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013;10(12):1213–8. doi: 10.1038/nmeth.2688 24097267; PubMed Central PMCID: PMC3959825.
73. Arendt D. The evolution of cell types in animals: emerging principles from molecular studies. Nat Rev Genet. 2008;9(11):868–82. doi: 10.1038/nrg2416 18927580.
74. Adamson B, Norman TM, Jost M, Cho MY, Nunez JK, Chen Y, et al. A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. Cell. 2016;167(7):1867–82 e21. doi: 10.1016/j.cell.2016.11.048 27984733; PubMed Central PMCID: PMC5315571.
75. Dixit A, Parnas O, Li B, Chen J, Fulco CP, Jerby-Arnon L, et al. Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. Cell. 2016;167(7):1853–66 e17. doi: 10.1016/j.cell.2016.11.038 27984732; PubMed Central PMCID: PMC5181115.
76. Wagner DE, Weinreb C, Collins ZM, Briggs JA, Megason SG, Klein AM. Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo. Science. 2018;360(6392):981–7. doi: 10.1126/science.aar4362 29700229; PubMed Central PMCID: PMC6083445.
77. Muguruma K, Nishiyama A, Kawakami H, Hashimoto K, Sasai Y. Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep. 2015;10(4):537–50. doi: 10.1016/j.celrep.2014.12.051 25640179.
78. Nayler SP, Becker EBE. The Use of Stem Cell-Derived Neurons for Understanding Development and Disease of the Cerebellum. Front Neurosci. 2018;12:646. doi: 10.3389/fnins.2018.00646 30319335; PubMed Central PMCID: PMC6168705.
79. Kanton S, Boyle MJ, He Z, Santel M, Weigert A, Sanchis-Calleja F, et al. Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature. 2019;574(7778):418–22. doi: 10.1038/s41586-019-1654-9 31619793.
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