Olig2 regulates terminal differentiation and maturation of peripheral olfactory sensory neurons

• Published in: Cellular and molecular life sciences : CMLS Vol. 77; no. 18; pp. 3597 - 3609
• Main Authors: Wang, Ya-Zhou, Fan, Hong, Ji, Yu, Reynolds, Kurt, Gu, Ran, Gan, Qini, Yamagami, Takashi, Zhao, Tianyu, Hamad, Salaheddin, Bizen, Norihisa, Takebayashi, Hirohide, Chen, YiPing, Wu, Shengxi, Pleasure, David, Lam, Kit, Zhou, Chengji J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-09-2020; Springer Nature B.V
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell differentiation; Cell fate; Central nervous system; Depletion; Differentiation; Fate maps; Gene mapping; Gestation; Helix-loop-helix proteins (basic); Life Sciences; Mapping; Maturation; Motor neurons; Nervous system; Neurogenesis; Neurons; Olfactory ensheathing cells; Olfactory marker protein; Olfactory receptor neurons; Olfactory system; Olig2 protein; Oligodendrocytes; Original Article; Sensory neurons; Smell; Dcx; Sox2; Basic helix–loop–helix (bHLH) transcription factors; Fabp7 (Blbp); Peripheral nervous system (PNS); Tuj1
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-019-03385-x

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.