Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons

Abstract

The bHLH transcription factor Olig2 is required for sequential cell fate determination of both motor neurons and oligodendrocytes and for progenitor proliferation in the central nervous system. However, the role of Olig2 in peripheral sensory neurogenesis remains unknown. We report that Olig2 is transiently expressed in the newly differentiated olfactory sensory neurons (OSNs) and is down-regulated in the mature OSNs in mice from early gestation to adulthood. Genetic fate mapping demonstrates that Olig2-expressing cells solely give rise to OSNs in the peripheral olfactory system. Olig2 depletion does not affect the proliferation of peripheral olfactory progenitors and the fate determination of OSNs, sustentacular cells, and the olfactory ensheathing cells. However, the terminal differentiation and maturation of OSNs are compromised in either Olig2 single or Olig1/Olig2 double knockout mice, associated with significantly diminished expression of multiple OSN maturation and odorant signaling genes, including Omp, Gnal, Adcy3, and Olfr15. We further demonstrate that Olig2 binds to the E-box in the Omp promoter region to regulate its expression. Taken together, our results reveal a distinctly novel function of Olig2 in the periphery nervous system to regulate the terminal differentiation and maturation of olfactory sensory neurons.

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Acknowledgements

We are grateful to David J. Anderson (HHMI and Caltech) for providing the Olig1/Olig2 frozen embryos, Jordan Hui, Ben Palmer, Arjun Stokes, Huan Zhao, Taylor Imai, Rebecca Duncan, Yue Liu, Santosh Kumar, Saharul Islam, Sarwat Amina and the rest of Zhou lab members for technical assistance or general support. This work was partially supported by grants from the NIH (R01DE021696, R01DE026737 and R01NS102261 to C.J.Z.), the Shriners Hospitals for Children (86600 and 85105 to C.J.Z., and postdoctoral fellowships to Y.Z.W. and R.G.), and the National Science Foundation of China (31970907 to Y.Z.W.). Q.G. and T.Y. received postdoctoral fellowships from the California Institute for Regenerative Medicine (CIRM) Stem Cell Training Program.

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Correspondence to Chengji J. Zhou.

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Wang, YZ., Fan, H., Ji, Y. et al. Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons. Cell. Mol. Life Sci. 77, 3597–3609 (2020). https://doi.org/10.1007/s00018-019-03385-x

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Keywords

  • Basic helix–loop–helix (bHLH) transcription factors
  • Peripheral nervous system (PNS)
  • Tuj1
  • Sox2
  • Fabp7 (Blbp)
  • Dcx