Transcription factors COUP-TFI and COUP-TFII are required for the production of granule cells in the mouse olfactory bulb.
Neural stem cells (NSCs) persist in the adult mammalian subventricular zone (SVZ) of the lateral ventricle. Primary NSCs generate rapidly dividing intermediate progenitor cells, which in turn generate neuroblasts that migrate along the rostral migratory stream (RMS) to the olfactory bulb (OB). Here, we have examined the role of the COUP-TFI and COUP-TFII orphan nuclear receptor transcription factors in mouse OB interneuron development. We observed that COUP-TFI is expressed in a gradient of low rostral to high caudal within the postnatal SVZ neural stem/progenitor cells. COUP-TFI is also expressed in a large number of migrating neuroblasts in the SVZ and RMS, and in mature interneurons in the OB. By contrast, very few COUP-TFII-expressing (+) cells exist in the SVZ-RMS-OB pathway. Conditional inactivation of COUP-TFI resulted in downregulation of tyrosine hydroxylase expression in the OB periglomerular cells and upregulation of COUP-TFII expression in the SVZ, RMS and OB deep granule cell layer. In COUP-TFI/COUP-TFII double conditional mutant SVZ, cell proliferation was increased through the upregulation of the proneural gene Ascl1. Furthermore, COUP-TFI/II-deficient neuroblasts had impaired migration, resulting in ectopic accumulation of calretinin (CR)+ and NeuN+ cells, and an increase in apoptotic cell death in the SVZ. Finally, we found that most Pax6+ and a subset of CR+ granular cells were lost in the OB. Taken together, these results suggest that COUP-TFI/II coordinately regulate the proliferation, migration and survival of a subpopulation of Pax6+ and CR+ granule cells in the OB.
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Xing
X
Zhou
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Fang
F
Liu
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Miao
M
Tian
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Zhejun
Z
Xu
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Qifei
Q
Liang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Chunyang
C
Wang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Jiwen
J
Li
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Zhidong
Z
Liu
Institute of Life Science, Nanchang University, Nanchang, Jiangxi Province 330031, China.
Ke
K
Tang
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Miao
M
He
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China yangz@fudan.edu.cn.
Zhengang
Z
Yang
D000818:Animals; D001973:Bromodeoxyuridine; D051838:COUP Transcription Factor I / Q000378:metabolism*; D051837:COUP Transcription Factor II / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D003094:Collagen; D004338:Drug Combinations; D005697:Galactosides; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry; D007211:Indoles; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D007797:Laminin; D051379:Mice; D008856:Microscopy, Fluorescence; D058953:Neural Stem Cells / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology*; D011509:Proteoglycans; D013629:Tamoxifen; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D051838:COUP Transcription Factor I; D051837:COUP Transcription Factor II; D004338:Drug Combinations; D005697:Galactosides; D007211:Indoles; D007797:Laminin; C497587:Nr2f2 protein, mouse; D011509:Proteoglycans; D013629:Tamoxifen; C059485:matrigel; D003094:Collagen; D014446:Tyrosine 3-Monooxygenase; D001973:Bromodeoxyuridine; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside
COUP-TFI (Nr2f1); COUP-TFII (Nr2f2); Interneurons; Neural stem cells; Neurogenesis; Olfactory bulb; SVZ