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miR-744 and miR-224 Downregulate Npas4 and Affect Lineage Differentiation Potential and Neurite Development During Neural Differentiation of Mouse Embryonic Stem Cells

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Abstract

Neuronal PAS domain protein 4 (Npas4) is a brain-specific transcription factor whose expression is enriched in neurogenic regions of the brain. In addition, it was demonstrated that Npas4 expression is dynamic and highly regulated during neural differentiation of embryonic stem cells (ESCs). While these findings implicate a role for Npas4 in neurogenesis, the underlying mechanisms of regulation remain unknown. Given that growing evidence suggests that microRNAs (miRNAs) play important roles in both embryonic and adult neurogenesis, we reasoned that miRNAs are good candidates for regulating Npas4 expression during neural differentiation of ESCs. In this study, we utilized the small RNA sequencing method to profile miRNA expression during neural differentiation of mouse ESCs. Two differentially expressed miRNAs were identified to be able to significantly reduce reporter gene activity by targeting the Npas4 3’UTR, namely miR-744 and miR-224. More importantly, ectopic expression of these miRNAs during neural differentiation resulted in downregulation of endogenous Npas4 expression. Subsequent functional analysis revealed that overexpression of either miR-744 or miR-224 delayed early neural differentiation, reduced GABAergic neuron production and inhibited neurite outgrowth. Collectively, our findings indicate that Npas4 not only functions at the early stages of neural differentiation but may also, in part, contribute to neuronal subtype specification and neurite development.

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References

  1. Flood WD, Moyer RW, Tsykin A, Sutherland GR, Koblar SA (2004) Nxf and Fbxo33: novel seizure-responsive genes in mice. Eur J Neurosci 20(7):1819–1826. doi:10.1111/j.1460-9568.2004.03646.x

    Article  PubMed  Google Scholar 

  2. Moser M, Knoth R, Bode C, Patterson C (2004) LE-PAS, a novel Arnt-dependent HLH-PAS protein, is expressed in limbic tissues and transactivates the CNS midline enhancer element. Mol Brain Res 128(2):141–149. doi:10.1016/j.molbrainres.2004.06.023

    Article  CAS  PubMed  Google Scholar 

  3. Ooe N, Saito K, Mikami N, Nakatuka I, Kaneko H (2004) Identification of a novel basic helix-loop-helix-PAS factor, NXF, reveals a Sim2 competitive, positive regulatory role in dendritic-cytoskeleton modulator Drebrin gene expression. Mol Cell Biol 24(2):608–616. doi:10.1128/mcb.24.2.608-616.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kewley RJ, Whitelaw ML, Chapman-Smith A (2004) The mammalian basic helix-loop-helix/PAS family of transcriptional regulators. Int J Biochem Cell Biol 36(2):189–204. doi:10.1016/s1357-2725(03)00211-5

    Article  CAS  PubMed  Google Scholar 

  5. Hester I, McKee S, Pelletier P, Thompson C, Storbeck C, Mears A, Schulz JB, Hakim AA, Sabourin LA (2007) Transient expression of Nxf, a bHLH-PAS transactivator induced by neuronal preconditioning, confers neuroprotection in cultured cells. Brain Res 1135(1):1–11. doi:10.1016/j.brainres.2006.11.083

    Article  CAS  PubMed  Google Scholar 

  6. Shamloo M, Soriano L, von Schack D, Rickhag M, Chin DJ, Gonzalez-Zulueta M, Gido G, Urfer R, Wieloch T, Nikolich K (2006) Npas4, a novel helix-loop-helix PAS domain protein, is regulated in response to cerebral ischemia. Eur J Neurosci 24(10):2705–2720. doi:10.1111/j.1460-9568.2006.05172.x

    Article  PubMed  Google Scholar 

  7. Lin Y, Bloodgood BL, Hauser JL, Lapan AD, Koon AC, Kim T-K, Hu LS, Malik AN, Greenberg ME (2008) Activity-dependent regulation of inhibitory synapse development by Npas4. Nature 455(7217):1198–1204. doi:10.1038/nature07319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhang S-J, Zou M, Lu L, Lau D, Ditzel DAW, Delucinge-Vivier C, Aso Y, Descombes P, Bading H (2009) Nuclear calcium signaling controls expression of a large gene pool: identification of a gene program for acquired neuroprotection induced by synaptic activity. PLoS Genet 5(8):e1000604. doi:10.1371/journal.pgen.1000604

    Article  PubMed  PubMed Central  Google Scholar 

  9. Spiegel I, Mardinly AR, Gabel HW, Bazinet JE, Couch CH, Tzeng CP, Harmin DA, Greenberg ME (2014) Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs. Cell 157(5):1216–1229. doi:10.1016/j.cell.2014.03.058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Leong WK, Klaric TS, Lin Y, Lewis MD, Koblar SA (2013) Upregulation of the neuronal Per-Arnt-Sim domain protein 4 (Npas4) in the rat corticolimbic system following focal cerebral ischemia. Eur J Neurosci 37(11):1875–1884. doi:10.1111/ejn.12163

    Article  PubMed  Google Scholar 

  11. Bloodgood BL, Sharma N, Browne HA, Trepman AZ, Greenberg ME (2013) The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature 503(7474):121–125. doi:10.1038/nature12743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pruunsild P, Sepp M, Orav E, Koppel I, Timmusk T (2011) Identification of cis-elements and transcription factors regulating neuronal activity-dependent transcription of human BDNF gene. J Neurosci 31(9):3295–3308. doi:10.1523/jneurosci.4540-10.2011

    Article  CAS  PubMed  Google Scholar 

  13. Ji W, Zhang X, Ji L, Wang K, Qiu Y (2015) Effects of brain-derived neurotrophic factor and neurotrophin-3 on the neuronal differentiation of rat adipose-derived stem cells. Mol Med Report 12(4):4981–4988. doi:10.3892/mmr.2015.4099

    CAS  Google Scholar 

  14. Lee J, Duan W, Mattson MP (2002) Evidence that brain‐derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J Neurochem 82(6):1367–1375. doi:10.1046/j.1471-4159.2002.01085.x

    Article  CAS  PubMed  Google Scholar 

  15. Vicario-Abejón C, Johe KK, Hazel TG, Collazo D, McKay RD (1995) Functions of basic fibroblast growth factor and neurotrophins in the differentiation of hippocampal neurons. Neuron 15(1):105–114. doi:10.1016/0896-6273(95)90068-3

    Article  PubMed  Google Scholar 

  16. Klaric TS, Thomas PQ, Dottori M, Leong WK, Koblar SA, Lewis MD (2014) A reduction in Npas4 expression results in delayed neural differentiation of mouse embryonic stem cells. Stem Cell Res Ther 5(3):64. doi:10.1186/scrt453

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mehler MF, Mattick JS (2007) Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiol Rev 87(3):799–823. doi:10.1152/physrev.00036.2006

    Article  CAS  PubMed  Google Scholar 

  18. Chekulaeva M, Filipowicz W (2009) Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol 21(3):452–460. doi:10.1016/j.ceb.2009.04.009

    Article  CAS  PubMed  Google Scholar 

  19. Flynt AS, Lai EC (2008) Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 9(11):831–842. doi:10.1038/nrg2455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chang T-C, Mendell JT (2007) microRNAs in vertebrate physiology and human disease. In: Annual Review of Genomics and Human Genetics, vol 8. Annual Review of Genomics and Human Genetics. pp 215–239. doi:10.1146/annurev.genom.8.080706.092351

  21. Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269. doi:10.1038/nrc1840

    Article  CAS  PubMed  Google Scholar 

  22. Hsu JB-K, Chiu C-M, Hsu S-D, Huang W-Y, Chien C-H, Lee T-Y, Huang H-D (2011) miRTar: an integrated system for identifying miRNA-target interactions in human. BMC Bioinformatics 12:300. doi:10.1186/1471-2105-12-300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5 (3). doi:2004/5/3/R13

  24. Krichevsky AM, Sonntag K-C, Isacson O, Kosik KS (2006) Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 24(4):857–864. doi:10.1634/stemcells.2005-0441

    Article  CAS  PubMed  Google Scholar 

  25. Packer AN, Xing Y, Harper SQ, Jones L, Davidson BL (2008) The bifunctional microRNA miR-9/miR-9*regulates REST and CoREST and is downregulated in Huntington’s disease. J Neurosci 28(53):14341–14346. doi:10.1523/jneurosci.2390-08.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cheng L-C, Pastrana E, Tavazoie M, Doetsch F (2009) miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci 12(4):399–408. doi:10.1038/nn.2294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Choi PS, Zakhary L, Choi W-Y, Caron S, Alvarez-Saavedra E, Miska EA, McManus M, Harfe B, Giraldez AJ, Horvitz RH, Schier AF, Dulac C (2008) Members of the miRNA-200 family regulate olfactory neurogenesis. Neuron 57(1):41–55. doi:10.1016/j.neuron.2007.11.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ivey KN, Srivastava D (2010) MicroRNAs as regulators of differentiation and cell fate decisions. Cell Stem Cell 7(1):36–41. doi:10.1016/j.stem.2010.06.012

    Article  CAS  PubMed  Google Scholar 

  29. Li X, Jin P (2010) Roles of small regulatory RNAs in determining neuronal identity. Nat Rev Neurosci 11(5):329–338. doi:10.1038/nrn2739

    Article  CAS  PubMed  Google Scholar 

  30. Liu S-P, Fu R-H, Yu H-H, Li K-W, Tsai C-H, Shyu W-C, Lin S-Z (2009) MicroRNAs regulation modulated self-renewal and lineage differentiation of stem cells. Cell Transplant 18(9):1039–1045. doi:10.3727/096368909x471224

    Article  PubMed  Google Scholar 

  31. Olsen L, Klausen M, Helboe L, Nielsen FC, Werge T (2009) MicroRNAs show mutually exclusive expression patterns in the brain of adult male rats. PLoS One 4(10):e7225. doi:10.1371/journal.pone.0007225

    Article  PubMed  PubMed Central  Google Scholar 

  32. Bersten DC, Wright JA, McCarthy PJ, Whitelaw ML (2014) Regulation of the neuronal transcription factor NPAS4 by REST and microRNAs. Biochim Biophys Acta 1839(1):13–24. doi:10.1016/j.bbagrm.2013.11.004

    Article  CAS  PubMed  Google Scholar 

  33. Hsu P-K, Xu B, Mukai J, Karayiorgou M, Gogos JA (2015) The BDNF Val66Met variant affects gene expression through miR-146b. Neurobiol Dis 77:228–237. doi:10.1016/j.nbd.2015.03.004

    Article  CAS  PubMed  Google Scholar 

  34. Ying Q-L, Stavridis M, Griffiths D, Li M, Smith A (2003) Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol 21(2):183–186. doi:10.1038/nbt780

    Article  CAS  PubMed  Google Scholar 

  35. Rathjen J, Lake J-A, Bettess MD, Washington JM, Chapman G, Rathjen PD (1999) Formation of a primitive ectoderm like cell population, EPL cells, from ES cells in response to biologically derived factors. J Cell Sci 112(5):601–612

    CAS  PubMed  Google Scholar 

  36. Ying Q-L, Smith AG (2003) Defined conditions for neural commitment and differentiation. Methods Enzymol 365:327–341. doi:10.1016/S0076-6879(03)65023-8

    Article  CAS  PubMed  Google Scholar 

  37. Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnetjourna 17:10–12

    Google Scholar 

  38. Griffiths-Jones S (2006) miRBase: the microRNA sequence database. In: MicroRNA Protocols. Springer, pp 129–138. doi:10.1385/1-59745-123-1:129

  39. Li H, Durbin R (2009) Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 25(14):1754–1760. doi:10.1093/bioinformatics/btp324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Anders S, Pyl PT, Huber W (2015) HTSeq-a Python framework to work with high-throughput sequencing data. Bioinformatics 31(2):166–169. doi:10.1093/bioinformatics/btu638

    Article  CAS  PubMed  Google Scholar 

  41. Robinson MD, McCarthy DJ, Smyth GK (2010) edgeR: a bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26(1):139–140. doi:10.1093/bioinformatics/btp616

    Article  CAS  PubMed  Google Scholar 

  42. Pool M, Thiemann J, Bar-Or A, Fournier AE (2008) NeuriteTracer: a novel ImageJ plugin for automated quantification of neurite outgrowth. J Neurosci Methods 168(1):134–139. doi:10.1016/j.jneumeth.2007.08.029

    Article  PubMed  Google Scholar 

  43. Stappert L, Roese-Koerner B, Bruestle O (2015) The role of microRNAs in human neural stem cells, neuronal differentiation and subtype specification. Cell Tissue Res 359(1):47–64. doi:10.1007/s00441-014-1981-y

    Article  CAS  PubMed  Google Scholar 

  44. Van Ooyen A (2005) Competition in neurite outgrowth and the development of nerve connections. In: VanPelt J, Kamermans M, Levelt CN, VanOoyen A, Ramakers GJA, Roelfsema PR (eds) Development, Dynamics and Pathology of Neuronal Networks: From Molecules to Functional Circuits, vol 147. Progress in Brain Research. pp 81–99. doi:10.1016/s0079-6123(04)47007-1

  45. Forrest AR, Kanamori-Katayama M, Tomaru Y, Lassmann T, Ninomiya N, Takahashi Y, de Hoon MJ, Kubosaki A, Kaiho A, Suzuki M (2010) Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation. Leukemia 24(2):460–466. doi:10.1038/leu.2009.246

    Article  CAS  PubMed  Google Scholar 

  46. Nachmani D, Lankry D, Wolf DG, Mandelboim O (2010) The human cytomegalovirus microRNA miR-UL112 acts synergistically with a cellular microRNA to escape immune elimination. Nat Immunol 11(9):806–813. doi:10.1038/ni.1916

    Article  CAS  PubMed  Google Scholar 

  47. Wu S, Huang S, Ding J, Zhao Y, Liang L, Liu T, Zhan R, He X (2010) Multiple microRNAs modulate p21Cip1/Waf1 expression by directly targeting its 3′ untranslated region. Oncogene 29(15):2302–2308. doi:10.1038/onc.2010.34

    Article  CAS  PubMed  Google Scholar 

  48. Yun J, Koike H, Ibi D, Toth E, Mizoguchi H, Nitta A, Yoneyama M, Ogita K, Yoneda Y, Nabeshima T, Nagai T, Yamada K (2010) Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice: possible involvement of a brain-specific transcription factor Npas4. J Neurochem 114(6):1840–1851. doi:10.1111/j.1471-4159.2010.06893.x

    Article  CAS  PubMed  Google Scholar 

  49. Klaric T, Lardelli M, Key B, Koblar S, Lewis M (2014) Activity-dependent expression of neuronal PAS domain-containing protein 4 (npas4a) in the develop zebrafish brain. Front Neuroanat 8:148. doi:10.3389/fnana.2014.00148

    PubMed  PubMed Central  Google Scholar 

  50. Gogolla N, LeBlanc JJ, Quast KB, Südhof TC, Fagiolini M, Hensch TK (2009) Common circuit defect of excitatory-inhibitory balance in mouse models of autism. J Neurodev Disord 1(2):172–181. doi:10.1007/s11689-009-9023-x

    Article  PubMed  PubMed Central  Google Scholar 

  51. Meechan DW, Tucker ES, Maynard TM, LaMantia A-S (2009) Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci U S A 106(38):16434–16445. doi:10.1073/pnas.0905696106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Morrow EM, Yoo S-Y, Flavell SW, Kim T-K, Lin Y, Hill RS, Mukaddes NM, Balkhy S, Gascon G, Hashmi A (2008) Identifying autism loci and genes by tracing recent shared ancestry. Science 321(5886):218–223. doi:10.1126/science.1157657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jessberger S, Gage FH (2014) Adult neurogenesis: bridging the gap between mice and humans. Trends Cell Biol 24(10):558–563. doi:10.1016/j.tcb.2014.07.003

    Article  PubMed  Google Scholar 

  54. Yun J, Nagai T, Furukawa-Hibi Y, Kuroda K, Kaibuchi K, Greenberg ME, Yamada K (2013) Neuronal Per Arnt Sim (PAS) domain protein 4 (NPAS4) regulates neurite outgrowth and phosphorylation of synapsin I. J Biol Chem 288(4):2655–2664. doi:10.1074/jbc.M112.413310

    Article  CAS  PubMed  Google Scholar 

  55. S-i Y, Takahashi H, Nishimura N, Kinoshita M, Asahina R, Kitsuki M, Tatsumi K, Furukawa-Hibi Y, Hirai H, Nagai T, Yamada K, Tsuboi A (2014) Npas4 regulates Mdm2 and thus Dcx in experience-dependent dendritic spine development of newborn olfactory bulb interneurons. Cell Rep 8(3):843–857. doi:10.1016/j.celrep.2014.06.056

    Article  Google Scholar 

  56. Roberts RC (2007) Schizophrenia in translation: disrupted in schizophrenia (DISC1): integrating clinical and basic findings. Schizophr Bull 33(1):11. doi:10.1093/schbul/sbl063

    Article  PubMed  Google Scholar 

  57. Bersten DC, Bruning JB, Peet DJ, Whitelaw ML (2014) Human variants in the neuronal basic Helix-Loop-Helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function. PLoS One 9(1):768. doi:10.1371/journal.pone.0085768

    Article  Google Scholar 

  58. Coutellier L, Beraki S, Ardestani PM, Saw NL, Shamloo M (2012) Npas4: a neuronal transcription factor with a key role in social and cognitive functions relevant to developmental disorders. PLoS One 7(9):6604. doi:10.1371/journal.pone.0046604

    Article  Google Scholar 

  59. Beveridge NJ, Cairns MJ (2012) MicroRNA dysregulation in schizophrenia. Neurobiol Dis 46(2):263–271. doi:10.1016/j.nbd.2011.12.029

    Article  CAS  PubMed  Google Scholar 

  60. Cho JA, Park H, Lim EH, Lee KW (2011) MicroRNA expression profiling in neurogenesis of adipose tissue-derived stem cells. J Genet 90(1):81–93. doi:10.1007/s12041-011-0041-6

    Article  CAS  PubMed  Google Scholar 

  61. Knelangen JM, van der Hoek MB, Kong W-C, Owens JA, Fischer B, Santos AN (2011) MicroRNA expression profile during adipogenic differentiation in mouse embryonic stem cells. Physiol Genomics 43(10):611–620. doi:10.1152/physiolgenomics.00116.2010

    Article  CAS  PubMed  Google Scholar 

  62. Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8(9):963–970. doi:10.1038/nm747

    Article  CAS  PubMed  Google Scholar 

  63. Lee S-T, Chu K, Jung K-H, Yoon H-J, Jeon D, Kang K-M, Park K-H, Bae E-K, Kim M, Lee SK (2010) MicroRNAs induced during ischemic preconditioning. Stroke 41(8):1646–1651. doi:10.1161/STROKEAHA.110.579649

    Article  PubMed  Google Scholar 

  64. Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M (2005) Combinatorial microRNA target predictions. Nat Genet 37(5):495–500. doi:10.1038/ng1536

    Article  CAS  PubMed  Google Scholar 

  65. Gribaudo S, Bovetti S, Friard O, Denorme M, Oboti L, Fasolo A, De Marchis S (2012) Transitory and activity‐dependent expression of neurogranin in olfactory bulb tufted cells during mouse postnatal development. J Comp Neurol 520(14):3055–3069. doi:10.1002/cne.23150

    Article  PubMed  Google Scholar 

  66. Ule J, Ule A, Spencer J, Williams A, Hu J-S, Cline M, Wang H, Clark T, Fraser C, Ruggiu M (2005) Nova regulates brain-specific splicing to shape the synapse. Nat Genet 37(8):844–852. doi:10.1038/ng1610

    Article  CAS  PubMed  Google Scholar 

  67. Blaesse P, Airaksinen MS, Rivera C, Kaila K (2009) Cation-chloride cotransporters and neuronal function. Neuron 61(6):820–838. doi:10.1016/j.neuron.2009.03.003

    Article  CAS  PubMed  Google Scholar 

  68. Xu B, Hsu P-K, Karayiorgou M, Gogos JA (2012) MicroRNA dysregulation in neuropsychiatric disorders and cognitive dysfunction. Neurobiol Dis 46(2):291–301. doi:10.1016/j.nbd.2012.02.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to thank David Lawrence for his preliminary work on RNA-seq data analysis. F.C.C was supported by the Adelaide Graduate Research Scholarship from the University of Adelaide.

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Authors and Affiliations

  1. School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia

    Fong Chan Choy, Thomas S. Klarić & Martin D. Lewis

  2. School of Medicine, The University of Adelaide, Adelaide, SA, Australia

    Simon A. Koblar

  3. South Australian Health & Medical Research Institute, North Terrace, Adelaide, SA, Australia

    Martin D. Lewis

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  1. Fong Chan Choy
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Choy, F.C., Klarić, T.S., Koblar, S.A. et al. miR-744 and miR-224 Downregulate Npas4 and Affect Lineage Differentiation Potential and Neurite Development During Neural Differentiation of Mouse Embryonic Stem Cells. Mol Neurobiol 54, 3528–3541 (2017). https://doi.org/10.1007/s12035-016-9912-4

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