The microcephaly gene Donson is essential for progenitors of cortical glutamatergic and GABAergic neurons
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Sathish Venkataramanappa aff001; Dagmar Schütz aff001; Friederike Saaber aff001; Praveen Ashok Kumar aff001; Philipp Abe aff001; Stefan Schulz aff001; Ralf Stumm aff001
Působiště autorů:
Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany
aff001
Vyšlo v časopise:
The microcephaly gene Donson is essential for progenitors of cortical glutamatergic and GABAergic neurons. PLoS Genet 17(3): e1009441. doi:10.1371/journal.pgen.1009441
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009441
Souhrn
Biallelic mutations in DONSON, an essential gene encoding for a replication fork protection factor, were linked to skeletal abnormalities and microcephaly. To better understand DONSON function in corticogenesis, we characterized Donson expression and consequences of conditional Donson deletion in the mouse telencephalon. Donson was widely expressed in the proliferation and differentiation zones of the embryonic dorsal and ventral telencephalon, which was followed by a postnatal expression decrease. Emx1-Cre-mediated Donson deletion in progenitors of cortical glutamatergic neurons caused extensive apoptosis in the early dorsomedial neuroepithelium, thus preventing formation of the neocortex and hippocampus. At the place of the missing lateral neocortex, these mutants exhibited a dorsal extension of an early-generated paleocortex. Targeting cortical neurons at the intermediate progenitor stage using Tbr2-Cre evoked no apparent malformations, whereas Nkx2.1-Cre-mediated Donson deletion in subpallial progenitors ablated 75% of Nkx2.1-derived cortical GABAergic neurons. Thus, the early telencephalic neuroepithelium depends critically on Donson function. Our findings help explain why the neocortex is most severely affected in individuals with DONSON mutations and suggest that DONSON-dependent microcephaly might be associated with so far unrecognized defects in cortical GABAergic neurons. Targeting Donson using an appropriate recombinase is proposed as a feasible strategy to ablate proliferating and nascent cells in experimental research.
Klíčová slova:
Apoptosis – Cerebrum – Hippocampus – Immunostaining – Neocortex – Neurons – Retinal ganglion cells – Piriform cortex
Zdroje
1. Mahmood S, Ahmad W, Hassan MJ. Autosomal Recessive Primary Microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum. Orphanet J Rare Dis. 2011;6:39. doi: 10.1186/1750-1172-6-39 21668957; PubMed Central PMCID: PMC3123551.
2. Naveed M, Kazmi SK, Amin M, Asif Z, Islam U, Shahid K, et al. Comprehensive review on the molecular genetics of autosomal recessive primary microcephaly (MCPH). Genet Res (Camb). 2018;100:e7. doi: 10.1017/S0016672318000046 30086807; PubMed Central PMCID: PMC6865151.
3. Alcantara D O’Driscoll M. Congenital microcephaly. Am J Med Genet C Semin Med Genet. 2014;166C(2):124–39. doi: 10.1002/ajmg.c.31397 24816482.
4. Duerinckx S, Abramowicz M. The genetics of congenitally small brains. Semin Cell Dev Biol. 2018;76:76–85. doi: 10.1016/j.semcdb.2017.09.015 28912110.
5. Huttner WB, Kosodo Y. Symmetric versus asymmetric cell division during neurogenesis in the developing vertebrate central nervous system. Curr Opin Cell Biol. 2005;17(6):648–57. doi: 10.1016/j.ceb.2005.10.005 16243506.
6. Hevner RF. Intermediate progenitors and Tbr2 in cortical development. J Anat. 2019;235(3):616–25. doi: 10.1111/joa.12939 30677129; PubMed Central PMCID: PMC6656625.
7. Miller DJ, Bhaduri A, Sestan N, Kriegstein A. Shared and derived features of cellular diversity in the human cerebral cortex. Curr Opin Neurobiol. 2019;56:117–24. doi: 10.1016/j.conb.2018.12.005 30677551.
8. Haubensak W, Attardo A, Denk W, Huttner WB. Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A. 2004;101(9):3196–201. doi: 10.1073/pnas.0308600100 14963232; PubMed Central PMCID: PMC365766.
9. Noctor SC, Martinez-Cerdeno V, Ivic L, Kriegstein AR. Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci. 2004;7(2):136–44. doi: 10.1038/nn1172 14703572.
10. Vasistha NA, Garcia-Moreno F, Arora S, Cheung AF, Arnold SJ, Robertson EJ, et al. Cortical and Clonal Contribution of Tbr2 Expressing Progenitors in the Developing Mouse Brain. Cereb Cortex. 2015;25(10):3290–302. doi: 10.1093/cercor/bhu125 24927931; PubMed Central PMCID: PMC4585488.
11. Lv X, Ren SQ, Zhang XJ, Shen Z, Ghosh T, Xianyu A, et al. TBR2 coordinates neurogenesis expansion and precise microcircuit organization via Protocadherin 19 in the mammalian cortex. Nat Commun. 2019;10(1):3946. doi: 10.1038/s41467-019-11854-x 31477701; PubMed Central PMCID: PMC6718393.
12. Marin O. Cellular and molecular mechanisms controlling the migration of neocortical interneurons. Eur J Neurosci. 2013;38(1):2019–29. Epub 2013/05/09. doi: 10.1111/ejn.12225 23651101.
13. Le Magueresse C, Monyer H. GABAergic interneurons shape the functional maturation of the cortex. Neuron. 2013;77(3):388–405. doi: 10.1016/j.neuron.2013.01.011 23395369.
14. Reynolds JJ, Bicknell LS, Carroll P, Higgs MR, Shaheen R, Murray JE, et al. Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism. Nat Genet. 2017;49(4):537–49. doi: 10.1038/ng.3790 28191891; PubMed Central PMCID: PMC5450907.
15. Rai R, Gu P, Broton C, Kumar-Sinha C, Chen Y, Chang S. The Replisome Mediates A-NHEJ Repair of Telomeres Lacking POT1-TPP1 Independently of MRN Function. Cell Rep. 2019;29(11):3708–25 e5. doi: 10.1016/j.celrep.2019.11.012 31825846; PubMed Central PMCID: PMC7001145.
16. Evrony GD, Cordero DR, Shen J, Partlow JN, Yu TW, Rodin RE, et al. Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome. Genome Res. 2017;27(8):1323–35. doi: 10.1101/gr.219899.116 28630177; PubMed Central PMCID: PMC5538549.
17. Karaca E, Posey JE, Bostwick B, Liu P, Gezdirici A, Yesil G, et al. Biallelic and De Novo Variants in DONSON Reveal a Clinical Spectrum of Cell Cycle-opathies with Microcephaly, Dwarfism and Skeletal Abnormalities. Am J Med Genet A. 2019;179(10):2056–66. doi: 10.1002/ajmg.a.61315 31407851; PubMed Central PMCID: PMC6936249.
18. Schulz S, Mensah MA, de Vries H, Frober R, Romeike B, Schneider U, et al. Microcephaly, short stature, and limb abnormality disorder due to novel autosomal biallelic DONSON mutations in two German siblings. Eur J Hum Genet. 2018;26(9):1282–7. doi: 10.1038/s41431-018-0128-0 29760432; PubMed Central PMCID: PMC6117362.
19. Knapp KM, Sullivan R, Murray J, Gimenez G, Arn P, D’Souza P, et al. Linked-read genome sequencing identifies biallelic pathogenic variants in DONSON as a novel cause of Meier-Gorlin syndrome. J Med Genet. 2020;57(3):195–202. doi: 10.1136/jmedgenet-2019-106396 31784481; PubMed Central PMCID: PMC7042968.
20. Abdelrahman HA, John A, Ali BR, Al-Gazali L. Further Delineation of the Microcephaly-Micromelia Syndrome Associated with Loss-of-Function Variants in DONSON. Mol Syndromol. 2019;10(3):171–6. doi: 10.1159/000497337 31191207; PubMed Central PMCID: PMC6528082.
21. Danyel M, Cheng Z, Jung C, Boschann F, Pantel JT, Hajjir N, et al. Differentiation of MISSLA and Fanconi anaemia by computer-aided image analysis and presentation of two novel MISSLA siblings. Eur J Hum Genet. 2019;27(12):1827–35. doi: 10.1038/s41431-019-0469-3 31320746; PubMed Central PMCID: PMC6871132.
22. Probst S, Daza RA, Bader N, Hummel JF, Weiss M, Tanriver Y, et al. A dual-fluorescence reporter in the Eomes locus for live imaging and medium-term lineage tracing. Genesis. 2017;55(8). Epub 2017/06/25. doi: 10.1002/dvg.23043 28646547; PubMed Central PMCID: PMC5568967.
23. Briata P, Di Blas E, Gulisano M, Mallamaci A, Iannone R, Boncinelli E, et al. EMX1 homeoprotein is expressed in cell nuclei of the developing cerebral cortex and in the axons of the olfactory sensory neurons. Mech Dev. 1996;57(2):169–80. Epub 1996/07/01. doi: 10.1016/0925-4773(96)00544-8 8843394.
24. Gorski JA, Talley T, Qiu M, Puelles L, Rubenstein JL, Jones KR. Cortical excitatory neurons and glia, but not GABAergic neurons, are produced in the Emx1-expressing lineage. J Neurosci. 2002;22(15):6309–14. doi: 20026564 12151506.
25. Hevner RF, Shi L, Justice N, Hsueh Y, Sheng M, Smiga S, et al. Tbr1 regulates differentiation of the preplate and layer 6. Neuron. 2001;29(2):353–66. doi: 10.1016/s0896-6273(01)00211-2 11239428.
26. Bielle F, Griveau A, Narboux-Neme N, Vigneau S, Sigrist M, Arber S, et al. Multiple origins of Cajal-Retzius cells at the borders of the developing pallium. Nat Neurosci. 2005;8(8):1002–12. doi: 10.1038/nn1511 16041369.
27. Takiguchi-Hayashi K, Sekiguchi M, Ashigaki S, Takamatsu M, Hasegawa H, Suzuki-Migishima R, et al. Generation of reelin-positive marginal zone cells from the caudomedial wall of telencephalic vesicles. J Neurosci. 2004;24(9):2286–95. Epub 2004/03/06. doi: 10.1523/JNEUROSCI.4671-03.2004 14999079; PubMed Central PMCID: PMC6730420.
28. Carney RS, Alfonso TB, Cohen D, Dai H, Nery S, Stoica B, et al. Cell migration along the lateral cortical stream to the developing basal telencephalic limbic system. J Neurosci. 2006;26(45):11562–74. Epub 2006/11/10. doi: 10.1523/JNEUROSCI.3092-06.2006 17093077; PubMed Central PMCID: PMC6674782.
29. Medina L, Abellan A. Development and evolution of the pallium. Semin Cell Dev Biol. 2009;20(6):698–711. Epub 2009/04/28. doi: 10.1016/j.semcdb.2009.04.008 19393324.
30. Medina L, Legaz I, Gonzalez G, De Castro F, Rubenstein JL, Puelles L. Expression of Dbx1, Neurogenin 2, Semaphorin 5A, Cadherin 8, and Emx1 distinguish ventral and lateral pallial histogenetic divisions in the developing mouse claustroamygdaloid complex. J Comp Neurol. 2004;474(4):504–23. doi: 10.1002/cne.20141 15174069.
31. Arlotta P, Molyneaux BJ, Chen J, Inoue J, Kominami R, Macklis JD. Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. Neuron. 2005;45(2):207–21. Epub 2005/01/25. doi: 10.1016/j.neuron.2004.12.036 15664173.
32. Britanova O, Alifragis P, Junek S, Jones K, Gruss P, Tarabykin V. A novel mode of tangential migration of cortical projection neurons. Dev Biol. 2006;298(1):299–311. Epub 2006/08/12. doi: 10.1016/j.ydbio.2006.06.040 16901480.
33. Britanova O, de Juan Romero C, Cheung A, Kwan KY, Schwark M, Gyorgy A, et al. Satb2 is a postmitotic determinant for upper-layer neuron specification in the neocortex. Neuron. 2008;57(3):378–92. Epub 2008/02/08. doi: 10.1016/j.neuron.2007.12.028 18255031.
34. Alcamo EA, Chirivella L, Dautzenberg M, Dobreva G, Farinas I, Grosschedl R, et al. Satb2 regulates callosal projection neuron identity in the developing cerebral cortex. Neuron. 2008;57(3):364–77. Epub 2008/02/08. doi: 10.1016/j.neuron.2007.12.012 18255030.
35. Bulchand S, Subramanian L, Tole S. Dynamic spatiotemporal expression of LIM genes and cofactors in the embryonic and postnatal cerebral cortex. Dev Dyn. 2003;226(3):460–9. Epub 2003/03/06. doi: 10.1002/dvdy.10235 12619132.
36. Vyas A, Saha B, Lai E, Tole S. Paleocortex is specified in mice in which dorsal telencephalic patterning is severely disrupted. J Comp Neurol. 2003;466(4):545–53. Epub 2003/10/21. doi: 10.1002/cne.10900 14566948.
37. Bayer SA. Neurogenesis in the rat primary olfactory cortex. Int J Dev Neurosci. 1986;4(3):251–71. Epub 1986/01/01. doi: 10.1016/0736-5748(86)90063-8 3455589.
38. Hevner RF, Daza RA, Englund C, Kohtz J, Fink A. Postnatal shifts of interneuron position in the neocortex of normal and reeler mice: evidence for inward radial migration. Neuroscience. 2004;124(3):605–18. Epub 2004/02/26. doi: 10.1016/j.neuroscience.2003.11.033 14980731.
39. Tiveron MC, Rossel M, Moepps B, Zhang YL, Seidenfaden R, Favor J, et al. Molecular interaction between projection neuron precursors and invading interneurons via stromal-derived factor 1 (CXCL12)/CXCR4 signaling in the cortical subventricular zone/intermediate zone. J Neurosci. 2006;26(51):13273–8. doi: 10.1523/JNEUROSCI.4162-06.2006 17182777.
40. Abe P, Molnar Z, Tzeng YS, Lai DM, Arnold SJ, Stumm R. Intermediate Progenitors Facilitate Intracortical Progression of Thalamocortical Axons and Interneurons through CXCL12 Chemokine Signaling. J Neurosci. 2015;35(38):13053–63. doi: 10.1523/JNEUROSCI.1488-15.2015 26400936.
41. Sessa A, Mao CA, Colasante G, Nini A, Klein WH, Broccoli V. Tbr2-positive intermediate (basal) neuronal progenitors safeguard cerebral cortex expansion by controlling amplification of pallial glutamatergic neurons and attraction of subpallial GABAergic interneurons. Genes Dev. 2010;24(16):1816–26. doi: 10.1101/gad.575410 20713522; PubMed Central PMCID: PMC2922508.
42. Lavdas AA, Grigoriou M, Pachnis V, Parnavelas JG. The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J Neurosci. 1999;19(18):7881–8. doi: 10.1523/JNEUROSCI.19-18-07881.1999 10479690.
43. Inta D, Alfonso J, von Engelhardt J, Kreuzberg MM, Meyer AH, van Hooft JA, et al. Neurogenesis and widespread forebrain migration of distinct GABAergic neurons from the postnatal subventricular zone. Proc Natl Acad Sci U S A. 2008;105(52):20994–9. Epub 2008/12/20. doi: 10.1073/pnas.0807059105 19095802; PubMed Central PMCID: PMC2605417.
44. Englund C, Fink A, Lau C, Pham D, Daza RA, Bulfone A, et al. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci. 2005;25(1):247–51. doi: 10.1523/JNEUROSCI.2899-04.2005 15634788; PubMed Central PMCID: PMC6725189.
45. Xu Q, Tam M, Anderson SA. Fate mapping Nkx2.1-lineage cells in the mouse telencephalon. J Comp Neurol. 2008;506(1):16–29. doi: 10.1002/cne.21529 17990269.
46. Sussel L, Marin O, Kimura S, Rubenstein JL. Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development. 1999;126(15):3359–70. Epub 1999/07/07. 10393115.
47. Nery S, Wichterle H, Fishell G. Sonic hedgehog contributes to oligodendrocyte specification in the mammalian forebrain. Development. 2001;128(4):527–40. Epub 2001/02/15. 11171336.
48. Turrero Garcia M, Harwell CC. Radial glia in the ventral telencephalon. FEBS Lett. 2017;591(24):3942–59. Epub 2017/09/02. doi: 10.1002/1873-3468.12829 28862741; PubMed Central PMCID: PMC5747302.
49. Miyoshi G, Butt SJB, Takebayashi H, Fishell G. Physiologically distinct temporal cohorts of cortical interneurons arise from telencephalic olig2-expressing precursors. Journal of Neuroscience. 2007;27(29):7786–98. doi: 10.1523/JNEUROSCI.1807-07.2007 WOS:000248177900017. 17634372
50. Kessaris N, Fogarty M, Iannarelli P, Grist M, Wegner M, Richardson WD. Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nat Neurosci. 2006;9(2):173–9. Epub 2006/01/03. doi: 10.1038/nn1620 16388308; PubMed Central PMCID: PMC6328015.
51. Dwyer ND, Chen B, Chou SJ, Hippenmeyer S, Nguyen L, Ghashghaei HT. Neural Stem Cells to Cerebral Cortex: Emerging Mechanisms Regulating Progenitor Behavior and Productivity. J Neurosci. 2016;36(45):11394–401. Epub 2016/12/03. doi: 10.1523/JNEUROSCI.2359-16.2016 27911741; PubMed Central PMCID: PMC5125206.
52. Chou SJ, Perez-Garcia CG, Kroll TT, O’Leary DD. Lhx2 specifies regional fate in Emx1 lineage of telencephalic progenitors generating cerebral cortex. Nat Neurosci. 2009;12(11):1381–9. Epub 2009/10/13. doi: 10.1038/nn.2427 19820705; PubMed Central PMCID: PMC2897740.
53. Klumper N, von Danwitz M, Stein J, Schmidt D, Schmidt A, Kristiansen G, et al. Downstream Neighbor of SON (DONSON) Expression Is Enhanced in Phenotypically Aggressive Prostate Cancers. Cancers (Basel). 2020;12(11). Epub 2020/11/25. doi: 10.3390/cancers12113439 33228112; PubMed Central PMCID: PMC7699366.
54. Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci. 2010;13(1):133–40. doi: 10.1038/nn.2467 20023653; PubMed Central PMCID: PMC2840225.
55. Costello I, Pimeisl IM, Drager S, Bikoff EK, Robertson EJ, Arnold SJ. The T-box transcription factor Eomesodermin acts upstream of Mesp1 to specify cardiac mesoderm during mouse gastrulation. Nat Cell Biol. 2011;13(9):1084–91. doi: 10.1038/ncb2304 21822279; PubMed Central PMCID: PMC4531310.
56. Saaber F, Schutz D, Miess E, Abe P, Desikan S, Ashok Kumar P, et al. ACKR3 Regulation of Neuronal Migration Requires ACKR3 Phosphorylation, but Not beta-Arrestin. Cell Rep. 2019;26(6):1473–88 e9. Epub 2019/02/07. doi: 10.1016/j.celrep.2019.01.049 30726732
57. Memi F, Abe P, Cariboni A, MacKay F, Parnavelas JG, Stumm R. CXC chemokine receptor 7 (CXCR7) affects the migration of GnRH neurons by regulating CXCL12 availability. J Neurosci. 2013;33(44):17527–37. Epub 2013/11/01. doi: 10.1523/JNEUROSCI.0857-13.2013 24174685; PubMed Central PMCID: PMC3812513.
58. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2007;445(7124):168–76. Epub 2006/12/08. doi: 10.1038/nature05453 17151600.
59. Kolodziej A, Schulz S, Guyon A, Wu DF, Pfeiffer M, Odemis V, et al. Tonic activation of CXC chemokine receptor 4 in immature granule cells supports neurogenesis in the adult dentate gyrus. J Neurosci. 2008;28(17):4488–500. Epub 2008/04/25. doi: 10.1523/JNEUROSCI.4721-07.2008 18434527; PubMed Central PMCID: PMC6670965.
60. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9(7):676–82. doi: 10.1038/nmeth.2019 22743772; PubMed Central PMCID: PMC3855844.
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