Skip to main content
Log in

bHLH transcription factors Hes1, Ascl1 and Oligo2 exhibit different expression patterns in the process of physiological electric fields-induced neuronal differentiation

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Recent studies have shown that the expression of bHLH transcription factors Hes1, Ascl1, and Oligo2 has an oscillating balance in neural stem cells (NSCs) to maintain their self-proliferation and multi-directional differentiation potential. This balance can be disrupted by exogenous stimulation. Our previous work has identified that electrical stimulation could induce neuronal differentiation of mouse NSCs.

Methods

To further evaluate if physiological electric fields (EFs)-induced neuronal differentiation is related to the expression patterns of bHLH transcription factors Hes1, Ascl1, and Oligo2, mouse embryonic brain NSCs were used to investigate the expression changes of Ascl1, Hes1 and Oligo2 in mRNA and protein levels during EF-induced neuronal differentiation.

Results

Our results showed that NSCs expressed high level of Hes1, while expression of Ascl1 and Oligo2 stayed at very low levels. When NSCs exited proliferation, the expression of Hes1 in differentiated cells began to decrease and oscillated at the low expression level. Oligo2 showed irregular changes in low expression level. EF-stimulation significantly increased the expression of Ascl1 at mRNA and protein levels accompanied by an increased percentage of neuronal differentiation. What’s more, over-expression of Hes1 inhibited the neuronal differentiation induced by EFs.

Conclusion

EF-stimulation directed neuronal differentiation of NSCs by promoting the continuous accumulation of Ascl1 expression and decreasing the expression of Hes1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255(5052):1707–1710

    Article  CAS  PubMed  Google Scholar 

  2. Malatesta P, Appolloni I, Calzolari F (2008) Radial glia and neural stem cells. Cell Tissue Res 331(1):165–178

    Article  PubMed  Google Scholar 

  3. Mccaig CD, Rajnicek AM, Song B, Zhao M (2005) Controlling cell behavior electrically: current views and future potential. Physiol Rev 85(3):943–978

    Article  PubMed  Google Scholar 

  4. Yu X, Meng X, Pei Z, Wang G, Liu R, Qi M, Zhou J, Wang F (2022) Physiological electric field: a potential construction regulator of human brain organoids. Int J Mol Sci 23(7):3877

    Article  PubMed  PubMed Central  Google Scholar 

  5. Meng X, Arocena M, Penninger J, Gage FH, Zhao M, Song B (2011) PI3K mediated electrotaxis of embryonic and adult neural progenitor cells in the presence of growth factors. Exp Neurol 227(1):210–217

    Article  CAS  PubMed  Google Scholar 

  6. Dong ZY, Pei Z, Li Z, Wang YL, Khan A, Meng XT (2017) Electric field stimulation induced neuronal differentiation of filum terminale derived neural progenitor cells. Neurosci Lett 651:109–115

    Article  CAS  PubMed  Google Scholar 

  7. Dong ZY, Pei Z, Wang YL, Li Z, Khan A, Meng XT (2019) Ascl1 regulates electric field-induced neuronal differentiation through PI3K/Akt pathway. Neuroscience 404:141–152

    Article  CAS  PubMed  Google Scholar 

  8. Zhu L, Yang S, Zheng L, Zhang G, Cheng G (2020) WNT/β-catenin pathway activation via Wnt1 overexpression and Axin1 downregulation correlates with cadherin-catenin complex disruption and increased lymph node involvement in micropapillary-predominant lung adenocarcinoma. J Thorac Dis 12(10):5906–5915

    Article  PubMed  PubMed Central  Google Scholar 

  9. Dennis DJ, Han S, Schuurmans C (2019) bHLH Transcription factors in neural development, disease, and reprogramming. Brain Res 1705:48–65

    Article  CAS  PubMed  Google Scholar 

  10. Imayoshi I, Isomura A, Harima Y, Kawaguchi K, Kori H, Miyachi H, Fujiwara T, Ishidate F, Kageyama R (2013) Oscillatory control of factors determining multipotency and fate in mouse neural progenitors. Science 342(6163):1203–1208

    Article  CAS  PubMed  Google Scholar 

  11. Imayoshi I, Kageyama R (2014) bHLH factors in self-renewal, multipotency, and fate choice of neural progenitor cells. Neuron 82(1):9–23

    Article  CAS  PubMed  Google Scholar 

  12. Imayoshi I, Sakamoto M, Yamaguchi M, Mori K, Kageyama R (2010) Essential roles of notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci 30(9):3489–3498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Meng XT, Du YS, Dong ZY, Wang GQ, Dong B, Guan XW, Yuan YZ, Pan H, Wang F (2020) Combination of electrical stimulation and bFGF synergistically promote neuronal differentiation of neural stem cells and neurite extension to construct 3D engineered neural tissue. J Neural Eng 17(5):056048

    PubMed  Google Scholar 

  14. Kageyama R, Ohtsuka T, Kobayashi T (2007) The hes gene family: repressors and oscillators that orchestrate embryogenesis. Development 134(7):1243–1251

    Article  CAS  PubMed  Google Scholar 

  15. Kobayashi T, Kageyama R (2010) Hes1 regulates embryonic stem cell differentiation by suppressing notch signaling. Genes Cells 15(7):689–698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Spitzer NC (2006) Electrical activity in early neuronal development. Nature 444(7120):707–712

    Article  CAS  PubMed  Google Scholar 

  17. Yamada M, Tanemura K, Okada S, Iwanami A, Nakamura M, Mizuno H, Ozawa M, Ohyama-Goto R, Kitamura N, Kawano M, Tan-Takeuchi K, Ohtsuka C, Miyawaki A, Takashima A, Ogawa M, Toyama Y, Okano H, Kondo T (2007) Electrical stimulation modulates fate determination of differentiating embryonic stem cells. Stem Cells 25(3):562–570

    Article  CAS  PubMed  Google Scholar 

  18. Park JS, Yang HN, Woo DG, Jeon SY, Do HJ, Huh SH, Kim NH, Kim JH, Park KH (2012) Exogenous Nurr1 gene expression in electrically-stimulated human MSCs and the induction of neurogenesis. Biomaterials 33(29):7300–7308

    Article  CAS  PubMed  Google Scholar 

  19. Leung AW, Murdoch B, Salem AF, Prasad MS, Gomez GA, García-Castro MI (2016) WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate. Development 143(3):398–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Toledo EM, Colombres M, Inestrosa NC (2008) Wnt signaling in neuroprotection and stem cell differentiation. Prog Neurobiol 86(3):281–296

    Article  CAS  PubMed  Google Scholar 

  21. Dixit R, Wilkinson G, Cancino GI, Shaker T, Adnani L, Li S, Dennis D, Kurrasch D, Chan JA, Olson EC, Kaplan DR, Zimmer C, Schuurmans C (2014) Neurog1 and Neurog2 control two waves of neuronal differentiation in the piriform cortex. J Neurosci 34(2):539–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Earley AM, Burbulla LF, Krainc D, Awatramani R (2021) Identification of ASCL1 as a determinant for human iPSC-derived dopaminergic neurons. Sci Rep 11(1):22257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Borrell V (2021) Protomapped by the pros: proneural factors pattern cortex folding. Neuron 109(18):2797–2799

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research was funded by The National Science Foundation of China, Grant Number 31371004.

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization, XM and ZD; experimental operation and analysis: ZL, HL and XY; writing-original draft preparation, ZL and HL; computer graphics, JZ; supervision, XM; funding acquisition, XM. ZL and HL contributed equally as first authors. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Xiaoting Meng.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Li, H., Yu, X. et al. bHLH transcription factors Hes1, Ascl1 and Oligo2 exhibit different expression patterns in the process of physiological electric fields-induced neuronal differentiation. Mol Biol Rep 51, 115 (2024). https://doi.org/10.1007/s11033-023-09118-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11033-023-09118-5

Keywords

Navigation