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A neuronal PI(3,4,5)P3-dependent program of oligodendrocyte precursor recruitment and myelination

Abstract

The molecular trigger of CNS myelination is unknown. By targeting Pten in cerebellar granule cells and activating the AKT1–mTOR pathway, we increased the caliber of normally unmyelinated axons and the expression of numerous genes encoding regulatory proteins. This led to the expansion of genetically wild-type oligodendrocyte progenitor cells, oligodendrocyte differentiation and de novo myelination of parallel fibers. Thus, a neuronal program dependent on the phosphoinositide PI(3,4,5)P3 is sufficient to trigger all steps of myelination.

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Figure 1: Pten mutant GC trigger de novo myelination of Pf axons.
Figure 2: Pten mutant GCs drive OPC proliferation in the ML.
Figure 3: Screening for candidate promyelinating factors and validation of Bdnf.

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References

  1. Nave, K.A. & Salzer, J.L. Curr. Opin. Neurobiol. 16, 492–500 (2006).

    Article  CAS  Google Scholar 

  2. Brinkmann, B.G. et al. Neuron 59, 581–595 (2008).

    Article  CAS  Google Scholar 

  3. Stiles, B., Groszer, M., Wang, S., Jiao, J. & Wu, H. Dev. Biol. 273, 175–184 (2004).

    Article  CAS  Google Scholar 

  4. Fünfschilling, U. & Reichardt, L.F. Genesis 33, 160–169 (2002).

    Article  Google Scholar 

  5. Lesche, R. et al. Genesis 32, 148–149 (2002).

    Article  CAS  Google Scholar 

  6. Gibson, E.M. et al. Science 344, 1252304 (2014).

    Article  Google Scholar 

  7. Karram, K. et al. Genesis 46, 743–757 (2008).

    Article  CAS  Google Scholar 

  8. Agarwal, A. et al. Cereb. Cortex 22, 1473–1486 (2012).

    Article  Google Scholar 

  9. Xiao, J. et al. Neurosignals 18, 186–202 (2010).

    Article  CAS  Google Scholar 

  10. Miron, V.E. et al. Nat. Neurosci. 16, 1211–1218 (2013).

    Article  CAS  Google Scholar 

  11. Le Bras, B. et al. Nat. Neurosci. 9, 340–348 (2006).

    Article  CAS  Google Scholar 

  12. Santra, M. et al. Glia 60, 1826–1838 (2012).

    Article  Google Scholar 

  13. Cruciat, C.M. & Niehrs, C. Cold Spring Harb. Perspect. Biol. 5, a015081 (2013).

    Article  Google Scholar 

  14. Sylva, M., Moorman, A.F. & van den Hoff, M.J. Birth Defects Res. C Embryo Today 99, 61–69 (2013).

    Article  CAS  Google Scholar 

  15. He, L. & Lu, Q.R. Neurosci. Bull. 29, 129–143 (2013).

    Article  CAS  Google Scholar 

  16. Markus, A., Zhong, J. & Snider, W.D. Neuron 35, 65–76 (2002).

    Article  CAS  Google Scholar 

  17. Lee, S. et al. Nat. Methods 9, 917–922 (2012).

    Article  CAS  Google Scholar 

  18. Katsanos, G.S. et al. Int. J. Immunopathol. Pharmacol. 21, 255–259 (2008).

    Article  CAS  Google Scholar 

  19. Ifergan, I. et al. Ann. Neurol. 70, 751–763 (2011).

    Article  CAS  Google Scholar 

  20. Yuen, T.J. et al. Cell 158, 383–396 (2014).

    Article  CAS  Google Scholar 

  21. Hirrlinger, P.G. et al. Mol. Cell. Neurosci. 30, 291–303 (2005).

    Article  CAS  Google Scholar 

  22. Li, L. et al. Oncogene 21, 4900–4907 (2002).

    Article  CAS  Google Scholar 

  23. Rauskolb, S. et al. J. Neurosci. 30, 1739–1749 (2010).

    Article  CAS  Google Scholar 

  24. Soriano, P. Nat. Genet. 21, 70–71 (1999).

    Article  CAS  Google Scholar 

  25. Lappe-Siefke, C. et al. Nat. Genet. 33, 366–374 (2003).

    Article  CAS  Google Scholar 

  26. Renier, N. et al. Cell 159, 896–910 (2014).

    Article  CAS  Google Scholar 

  27. Bormuth, I. et al. J. Neurosci. 33, 641–651 (2013).

    Article  CAS  Google Scholar 

  28. Rossner, M.J. et al. J. Neurosci. 26, 9956–9966 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to A. Fahrenholz, U. Bode, C. Stuenkel and H.N. Hidaji for technical support and thank T. Ruhwedel and W. Moebius for help with electron microscopy. We thank U. Fünfschilling and L. Reichardt (University of California, San Francisco) for Tg(mα6)-Cre mice, H. Wu (University of California at Los Angeles School of Medicine) for Pten loxP-flanked mice, M. Sendtner (University of Würzburg) for Bdnf loxP-flanked mice, C. Birchmeier (Max-Delbrück-Center for Molecular Medicine, Berlin) for Nrg1 loxP-flanked mice, P. Soriano (Icahn School of Medicine at Mount Sinai, New York) for Rosa26-lacZ reporter mice, J. Trotter (Johannes Gutenberg University, Mainz) for Ng2-EYFP mutants, F. Kirchhoff (University of Saarland, Homburg) for Plp1-DsRed transgenic mice, B. Emery (Oregon Health and Science University, Portland) for a Myrf in situ hybridization probe, and S. Ghandour (University of Strasbourg) and J. Alberta (Dana-Farber Cancer Institute, Boston) for primary antibodies. This work was supported by grants from the German Research Foundation (KFO241 to M.J.R., GO 2463/1-1 to S.G. and SPP-1172 to K.-A.N.) and by an ERC Advanced grant to K.-A.N.

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Authors and Affiliations

Authors

Contributions

S.G. and K.-A.N. developed the study concept and design. A.P., B.W., O.Y., J.M.E., K.K. and G.L.W. performed immunoblotting, immunohistochemistry, cell culture analyses and electron microscopy under the supervision of S.G. K.Y. performed in situ hybridization. N.R. performed volume imaging under the supervision of M.T.-L. G.L.W. and S.P.W. performed laser-capture microdissection and subsequent microarray hybridization under the supervision of M.J.R. S.S. performed electrophysiological recordings under the supervision of R.T.K. A.A. generated Nex-CreERT2 mutant mice. S.G., G.L.W., R.T.K. and K.-A.N. wrote the manuscript. All authors contributed to and approved the manuscript.

Corresponding author

Correspondence to Klaus-Armin Nave.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Progressive enlargement of Pten mutant GC and Pf

(a) Conditional ablation of Pten in early postnatal GC causes progressive cerebellar enlargement as visualized by H&E staining (ages are indicated). Images are representative of 3 similar experiments.

(b) Immunostaining for GABAA receptor α6 subunit (in red), a cerebellar GC marker, at the indicated ages. Increased cell size in the mutants is indicated by dashed lines. Images are representative of 3 similar experiments.

(c) Progressive enlargement of Pf calibers in the mutant ML over time as determined by EM (n=3 per genotype and age, 140 Pf quantified per animal).

Supplementary Figure 2 Pten mutant mice as a model of Lhermitte-Duclos disease

(a) Gallyas silver impregnation of cerebellar parasagittal sections reveals a focal pathology (asterisks) in aged Pten mutants, preferentially localized to the inferior lobe (IL) and the posterior lobe (PL). Pathology is characterized by secondary focal hypergrowth of GC immunostained for NeuN (arrowheads in b; age 1 year; boxed area magnified on the right), loss of Purkinje cells immunostained for Calbindin (arrowheads in c; age, 1 year; boxed area magnified on the right), loss of central white matter immunostained for CNP (arrowheads in d; age, 1 year; boxed area magnified on the right), and presence of activated microglia cells immunostained for Mac-3 (in e; age, 1.5 years; boxed area magnified on the right) and enhanced vascularization (boxed area in e magnified on the right and further magnified in inset). Cerebellar lobes I-X are marked in c. Images are representative of >3 similar experiments.

Supplementary Figure 3 Progressive ectopic myelination in the ML

(a) Gallyas silver impregnation of myelinated fibers in control (top) and Pten mutant (bottom) cerebellum at the indicated ages.

(b) Immunostaining for CNP (green) of control (top) and mutant (bottom) cerebellum at the indicated ages.

GL, granule cell layer; ML, molecular layer; PL, Purkinje cell layer. Images are representative of >3 similar experiments.

Supplementary Figure 4 Pf synapses onto Purkinje cell dendrites in the presence of myelin

EM images of myelinated Pf in mutants at 1 year of age. The “en passant” synapses of Pf on Purkinje cells spines are restricted to nodal regions. Arrowheads point to presynaptic vesicles. M, myelin; Pf, parallel fiber axon; Pn, paranodal loop; s, dendritic spine. Images are representative of >3 similar experiments.

Supplementary Figure 5 Glutamate signaling and Pf spiking activity of mutant granule cells are not altered

(a-c) Responses of voltage-clamped OPCs in ML to 30μM kainate (a), 20μM AMPA (b) and 60μM NMDA (c).

(d-f) The amplitude of the glutamate agonist-evoked currents in OPCs of ML plotted against the age of animal. Slopes are not significantly different between control (blue) and mutant (red) for kainate-evoked currents (control n=48 cells from 21 animals of 12 litters, mutant n=42 cells from 18 animals of 10 litters; p=0.67, d.f.=68, F=0.1823) (d), AMPA-evoked currents (control n=25 cells from 11 animals of 5 litters, mutant n=21 cells from 7 animals of 3 litters; p=0.178, d.f.=42, F=1.876) (e) and NMDA-evoked currents (control n=16 cells from 10 animals of 7 litters, mutant n=17 cells from 10 animals of 7 litters; p=0.5543, d.f.=29, F=0.3579, all linear regressions) (f).

(g-i) The average amplitudes of glutamate-evoked currents are not significantly different between control (blue) and mutant mice (red) for kainate-evoked currents (control n=48 cells from 21 animals of 12 litters, mutant n=42 cells from 18 animals of 10 litters; p=0.589, t=0.5423, d.f.=88) (g), AMPA-evoked currents (control n=25 cells from 11 animals of 5 litters, mutant n=21 cells from 7 animals of 3 litters; p=0.268, t=1.122, d.f.=44) (h) and NMDA-evoked currents (control n=16 cells from 10 animals of 7 litters, mutant n=17 cells from 10 animals of 7 litters; p=0.651, t=0.457, d.f.=31, all two-tailed unpaired Student’s t-test) (i).

(j) Resting membrane potential is not significantly different between control (blue) and mutant mice (red) (control n=120 cells from 30 animals of 14 litters, mutant n=71 cells from 26 animals of 13 litters; p=0.159, t=1.414, d.f.=189, two-tailed unpaired Student’s t-test).

(k-m) Synaptic input in OPCs of the ML does not differ in frequency (control n=42 cells from 25 animals of 12 litters, mutant=28 cells from 17 animals of 11 litters; p=0.1248, t=1.554, d.f.=68) (k) or amplitude (control n=42 cells from 25 animals of 12 litters, mutant n=28 cells from 25 animals of 12 litters; p=0.5973, t=0.5308, d.f.=68) (l) between control (blue) and mutant mice (red). Slopes are not significantly different between control (n=42 cells from 25 animals of 12 litters) and mutant mice (n=28 cells from 25 animals of 12 litters; p=0.1976, d.f.=66, F=1.694) for regression between amplitude of synaptic input and age (m).

(n) Spontaneous synaptic currents (a), representative single synaptic events (b), recorded in voltage-clamped Purkinje cells in control and mutant mice. (c) Amplitudes of synaptic events are not significantly different between control (blue, n=5 cells from 2 animals of 1 litter) and mutant mice (red, n=4 cells from 1 animal) in Purkinje cells (p=0.9748, t=0.0327, d.f.=7).

Data are means ± s.e.m. All proportions presented below bar graphs had a p>0.05; chi-square test (in g-i, and k). By analysis of Covariance (ANCOVA) slopes of linear regression lines were not significantly different between conditions (p>0.05 in d,e,f, and m).

Supplementary Figure 6 Targeted ablation of Pten in a small subset of cerebellar GC

(a) Tamoxifen treatment of Nex-CreERT2;Rosa26-lacZ mutant mice induces Cre-mediated activation of a lacZ reporter gene in a small subset of GC.

(b) Tamoxifen treatment scheme of Nex-CreERT2 ;PtenloxP/loxP mutant mice.

(c-f) Nex-CreERT2 ;PtenloxP/loxP mutants exhibit significantly more CNP+ oligodendrocytes (p< 0.0001, t=19, d.f.=4) and a larger MBP+ area (p=0.009 t=4.739, d.f.=4) in the ML when compared to controls (quantitated in parasagittal sections of the cerebellar vermis; n=3 mice each genotype; age, 30 weeks).

Data are means ± s.e.m. **p<0.01; ***p<0.001, two-tailed unpaired Student’s t-test. GL, GC layer; ML, molecular layer; WM, White matter. Images in a, c and e are representative of 3 similar experiments.

Supplementary Figure 7 Neuregulin-1 is not required for Pf myelination

(a,b) Double mutant mice lacking both Pten and Nrg1 in cerebellar GC (Pten cKO;Nrg1 cKO) do not differ from single Pten mutants (Pten cKO) in the number of CNP+ oligodendrocytes (in a, Control vs. Pten cKO;Nrg1 het, p=0.0664, t=2.505; Control vs. Pten cKO, p<0.0001, t=13.02; Pten cKO vs. Pten cKO;Nrg1 cKO, p=0.1068, t=1.896, d.f.=13, F=48.06) and in the MBP+ myelinated area (in b, Control vs. Pten cKO;Nrg1 het, p=0.8735, t=0.1696; Control vs. Pten cKO, p<0.0001, t=12.76; Pten cKO vs. Pten cKO;Nrg1 cKO, p=0.0982, t=1.956, d.f.=13, F=26.11) of the ML. Quantified were parasagittal sections of the cerebellar vermis (n=3-4 mice each genotype; 10 weeks of age).

(c,d) G-ratio analysis of EM data sets from Pten cKO and Pten cKO;Nrg1 cKO mutants (n=3 mice each genotype; 10 weeks of age). Myelin sheath thickness is unchanged (p=0.0581, t=2.631, d.f.=4).

(e) Comparison of the axon caliber of myelinated (p=0.1198, t=1.972, d.f.=4) and unmyelinated (p=0.4224, t=0.8928, d.f.=4) Pf in mice of both genotypes (n=3 mice each genotype; 10 weeks of age) shows no significant difference.

Data are means ± s.e.m. ***p<0.001, two-tailed unpaired Student’s t-test (d,e) or one-way analysis of variance (ANOVA) followed by Bonferroni test (a,b).

Supplementary Figure 8 Functional validation of selected candidate factors

a-d: OPC proliferation assay (neuron/oligodendrocyte cocultures):

(a) Representative images of spinal cord coculture (25 days in vitro) treated with recombinant proteins and immunostained for Olig2 (in green). Cell nuclei counterstained with DAPI (pseudocolored in red). Oligodendrocyte lineage cells appear yellow (quantified in b). Images are representative of 3 to 5 similar experiments.

(b) Quantitation of Olig2+ cells after treatment of cocultures with the indicated factors between DIV 12 and DIV 25 (n=3 to 4 independent coculture experiments; Pdgf: p=0.0113; Sparcl1: p=0.9947; Vegfc: p=0.3451; Fgf1: p=0.0179; Pleiotrophin: p=0.4774; Tmsb4x: p=0.3125; Timp3: p=0.1766; Activin A: p=0.0869). The percentage of Olig2+ cells was calculated relative to the cell number determined by DAPI and normalized to vehicle treated cultures (set to 100%, dashed lines). The known OPC mitogen Pdgf was used as positive control. Note the increase in the number of Olig2+ cells after treatment with Fgf1.

(c,d) Confirmation of Fgf1 as a mitogen for OPCs. Representative images of cocultures treated with vehicle (top) or Fgf1 (bottom) and costained for Olig2 (red, in c) and Ki67 (green, in c). Percentage of Ki67+, Olig2+ cells after Fgf1 treatment is quantitated in d (n=4 independent experiments per condition, p= p=0.0153, t=5.013, d.f.=3).

e,f: Oligodendrocyte differentiation assay (neuron-free mixed glial cultures):

(e) Representative images of primary oligodendrocytes in a mixed glial culture co-immunostained for MBP and GFAP (left) or Olig2 and Apc-CC1 (right) 3 days after plating. Images are representative of 5 similar experiments.

(f) Quantitation of the percentage of CC1 expressing oligodendrocytes in relation to Olig2+ cells after 3 (Vehicle vs. Klotho, p=0.5403, Vehicle vs. Pleiotrophin, p=0.2397, Vehicle vs. Timp3, p=0.5629, Vehicle vs. Activin, p=0.0003) and 5 days (Vehicle vs. Klotho, p=0.6483, Vehicle vs. Pleiotrophin, p=0.8878, Vehicle vs. Timp3, p=0.7308, Vehicle vs. Activin, p=0.0026) treatment with either vehicle or one of the indicated recombinant proteins (n=3-5 independent experiments each group). Note the activity of Activin A as a differentiation factor.

g,h: Myelination assay (neuron/oligodendrocyte cocultures):

(g) Representative image of a myelinating spinal cord coculture (25 days in vitro) immunostained for MBP (in green) and Smi31 (in red). The image is representative of >10 similar experiments.

(h) The ensheathment/myelination index was calculated by dividing the MBP+ area of myelin by the Smi31+ area of axons (using single channel images) and defining this ratio as 1.0 in vehicle treated controls (dashed line). Note the pro-myelinating activity of 5 factors in this assay, which was not optimized for concentrations and treatment times. Number of independent experiments per condition: n=3 for Vegfc (p=0.8806), and Tmsb4x (p=0.025), n=5 for Sparcl1 (p=0.5781) and Fgf1 (p=0.0498), n=11 for Pdgf (p=0.0049), Ptn (p=0.0005), Timp3 (p=0.0264) and Activin A (p=0.0132).

(i) Mixed neuron-free glial cultures treated for 3 days with Activin A in combination with either 2.5 μM SIS3 (SI), 0.5 μM LY294002 (LY) or 10 μM UO126 (UO) were immunostained as in (e) and statistically analyzed for the ratio of CC1 to Olig2+ cells (n=3 to 6 independent experiments per condition). Note the requirement of MAPK (ERK 1/2) (UO) in Activin A-stimulated oligodendrocyte differentiation (Vehicle vs. Vehicle+SI: p=0.8215, t=0.2828; Vehicle vs. Vehicle+LY: p=0.1509, t=1.953; Vehicle vs. Vehicle + UO: p=0.0674, t=2.193; Activin A vs. Activin A+SI: p=0.3050, t=1.01; Activin A vs. Activin A+LY: p=0.9959, t=0.0521; Activin A vs. Activin A+UO: p=0.0005 t=4.751; d.f.=29; F=12.47)

Data are means ± s.e.m. *p<0.05; **p<0.01; ***p<0.001, Wilcoxon matched pairs test (in b,d,f,h), or one-way analysis of variance (ANOVA) followed by Bonferroni test (in i).

Supplementary Figure 9 Fgf1 treatment of spinal cord cocultures

Different from other factors tested (in Supplementary Fig.8g,h) Fgf1 caused oligodendrocytes to elaborate myelin-like flat membrane sheaths, that can be immunostained for MBP (white/green) but largely fail to myelinate axons (labeled with Smi31, red). Images are representative of 5 similar experiments.

Supplementary Figure 10 Microglia, astrocytes and vascular endothelia cells in Pten mutant mice

(a-c) Numbers of microglial cells stained for Iba1 (in a) or Mac-3 (in b) are increased in the ML (in a: p=0.0413, t=3.184, d.f.=4; in b: p=0.0295, t=3.315, d.f.=4) but not in the GL (in a: p=0.5484, t=0.912, d.f.=4; in b: p=0.9888, t=0.015, d.f.=4) of Pten mutant mice. Likewise, the area of GFAP+ astrocytes is increased in the mutant ML (p=0.0406, t=2.983, d.f.=4) but not in GL (p=0.141, t=1.831, d.f.=4) (in c). Arrowheads (in a) point to single Iba1+ cells.

(d) The area covered by vascular endothelial cells is increased in the mutant GL compared to controls as quantitated in lobe 5 (p=0.0498, t=2.78, d.f.=4).

n=3 mice each genotype; age: 2.5 months. Data are means ± s.e.m. *p<0.05, two-tailed unpaired Student’s t-test. GL, GC layer; ML, molecular layer. Images (in a and d) are representative of 3 similar experiments.

Supplementary Figure 11 No signs of gliosis in NEX-CreERT2;PtenloxP/loxP mice

Upon sparse recombination, Nex-CreERT2 ;PtenloxP/loxP mutants show no increase of Iba1+ (in a) or Mac-3+ microglial cells (in b) when compared to controls in ML (in a: p=0.8886, t=0.1523, d.f.=4; in b: p=0,1494, t=1.782, d.f.=4) and GL (in a: p=0.516, t=0.7343, d.f.=4; in b: p=0,7067, t=0.4042, d.f.=4). Also the GFAP+ astroglial area is similar in mutants and controls (in c: ML: p=0.4998, t=0.7652, d.f.=4; GL: p=0.9487, t=0.6992, d.f.=4). Arrowheads (in a) indicate single Iba1+ cells.

Quantitations were performed on parasagittal sections of the cerebellar vermis (n=3 mice each genotype; age 30 weeks). Data are means ± s.e.m. Two-tailed unpaired Student’s t-test. GL, GC layer; ML, molecular layer. Images (in a) are representative of 3 similar experiments.

Supplementary Figure 12 Conditional inactivation of Pten in principal neurons of the hippocampus

(a,b) Tamoxifen treatment schemes for Nex-CreERT2;Rosa26-lacZ mice (a, top), as used for Cre-mediated activation of lacZ in CA3 pyramidal neurons (image in b is representative of 3 similar experiments.), and for conditional Pten mutants (a, bottom) used for histological analysis (see below).

(c-e) Nex-CreERT2 ;PtenloxP/loxP mutants exhibit the same number of CNP+ oligodendrocytes (arrowheads in c; quantified in d, p=0.8451, t=0.2084, d.f.=4), and a similar (MBP+) myelinated area in the hippocampus (p=0.7849, t=0.2918, d.f.=4) when compared to controls (in e, quantified on coronal sections of the forebrain; n=3 mice each genotype and age). Data are means ± s.e.m. **p<0.01; ***p<0.001, two-tailed unpaired Student’s t-test. CC, corpus callosum; DG, dentate gyrus. Images are representative of 3 similar experiments.

(f-g) Hippocampal CA3 neurons from Nex-CreERT2 ;PtenloxP/loxP mutants are enlarged in size, when quantified in H&E stained paraffin sections (in f, n=3 per genotype; 40 cells per animal, p=0.0005, t=10.18, d.f.=4) and by electron microscopy (in g, n=2 per genotype; 10-15 cells per animal).

Data are means ± s.e.m. ***p<0.001, two-tailed unpaired Student’s t-test. Images are representative of 2 (in g) or 3 (in b,c and f) similar experiments.

Supplementary Figure 13 Full length blots for data shown in Figure 1.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–13, Supplementary Notes, and Supplementary Table 1 (PDF 3195 kb)

Supplementary Methods Checklist (PDF 570 kb)

A Tg(mα6)-Cre*PtenloxP/loxP mutant mouse at the age of 3.5 months

Young mutants appear behaviorally normal. (MOV 1463 kb)

A Tg(mα6)-Cre*PtenloxP/loxP mutant mouse at the age of 15 months

Aged mutants develop ataxia and tremor. (MOV 2816 kb)

Whole-mount immunolabeling of the cerebellum combined with light-sheet and 2-photon microscopy

iDISCO whole-mount anti-CNP immunohistochemistry on a control and a mutant mouse cerebellum (age of 4.5 months) and subsequent analysis by light-sheet and 2-photon microscopy. (MP4 143021 kb)

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Goebbels, S., Wieser, G., Pieper, A. et al. A neuronal PI(3,4,5)P3-dependent program of oligodendrocyte precursor recruitment and myelination. Nat Neurosci 20, 10–15 (2017). https://doi.org/10.1038/nn.4425

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