Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons
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Cellular and Molecular Life Sciences
ORIGINAL ARTICLE
Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons Ya‑Zhou Wang1,2 · Hong Fan1 · Yu Ji2,3 · Kurt Reynolds2,3 · Ran Gu2,3 · Qini Gan2 · Takashi Yamagami2 · Tianyu Zhao2 · Salaheddin Hamad2 · Norihisa Bizen4 · Hirohide Takebayashi4 · YiPing Chen5 · Shengxi Wu1 · David Pleasure2 · Kit Lam3 · Chengji J. Zhou2,3 Received: 11 June 2019 / Revised: 8 November 2019 / Accepted: 12 November 2019 © Springer Nature Switzerland AG 2019
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. Keywords Basic helix–loop–helix (bHLH) transcription factors · Peripheral nervous system (PNS) · Tuj1 · Sox2 · Fabp7 (Blbp) · Dcx
Introduction Ya-Zhou Wang, Hong Fan, and Yu Ji contribute equally. * Chengji J. Zhou [email protected] 1
Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, 169 Chang Le Xi Road, Xi’an 710032, Shaanxi, China
2
Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children, University of California at Davis, School of Medicine, 2425 Stockton Blvd., Sacramento, CA 95817, USA
3
Department of Biochemistry and Molecular Medicine, University of California at Davis, School of Medicine, 2425 Stockton Blvd., Sacramento, CA 95817, USA
4
Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi, Chuo‑ku, Niigata 951‑8510, Japan
5
Department of Cell and Molecular Biology, Tulane University, New Orleans, LA 70118, USA
Neuronal differentiation is a multi-step process involving cell fate specification, progenitor expansion, and terminal maturation. Transcrip
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