Astroglial β-Arrestin1-mediated Nuclear Signaling Regulates the Expansion of Neural Precursor Cells in Adult Hippocampus.
Adult hippocampal neurogenesis is crucial for preserving normal brain function, but how it is regulated by niche cells is uncertain. Here we show that β-arrestin 1 (β-arr1) in dentate gyrus (DG) regulates neural precursor proliferation. β-arr1 knockout (KO) mice show reduced neural precursor proliferation in subgranular zone (SGZ) which could be rescued by selective viral expression of β-arr1 but not its nuclear-function-deficient mutants under control of hGFAP promotor in DG. Compared with wild type astrocytes, β-arr1 KO astrocytes nurture less neurospheres, and this may be attributed to changed activity of soluble, heat-sensitive excretive factors, such as BMP2. RNA-sequencing reveals that β-arr1 KO DG astrocytes exhibit an aberrant gene expression profile of niche factors, including elevated transcription of Bmp2. Taken together, our data suggest that β-arr1 mediated nuclear signaling regulates the production of excretive factors derived from niche astrocytes and expansion of neural precursors in DG, thus maintaining homeostasis of adult hippocampal neurogenesis.
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Yezheng
Y
Tao
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Li
L
Ma
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Zhaohui
Z
Liao
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Qiumin
Q
Le
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Jialing
J
Yu
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Xing
X
Liu
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Haohong
H
Li
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Yuejun
Y
Chen
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Ping
P
Zheng
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Zhengang
Z
Yang
The State Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, the Institutes of Brain Science, and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Lan
L
Ma
D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology*; D015398:Signal Transduction; D059467:Transcriptome; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
C000605255:Arrb1 protein, mouse; D019390:Arrestins; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins