Abstract
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.
Highlights
Several niche determinants, for example, neurotransmitters such as glutamate, GABA and dopamine, non-neurotransmitters such as bone morphogenetic proteins (BMPs), sonic hedgehog (Shh), Notch, Wnt, Wnt inhibitor, growth factors, and neurotrophic factors have been found involved in adult neural precursors-niche interaction[6]
We demonstrate that β -arr[1] in dentate gyrus (DG) participates in adult hippocampal neurogenesis
We further propose that β -arr1-mediated signaling in niche astrocytes enhances the mitotic expansion of neural precursors in adult hippocampus and this may involve nuclear β -arr1-mediated transcription of excretive niche factors, such as BMP2, from astrocytes in neurogenic niche
Summary
For example, neurotransmitters such as glutamate, GABA and dopamine, non-neurotransmitters such as bone morphogenetic proteins (BMPs), sonic hedgehog (Shh), Notch, Wnt, Wnt inhibitor, growth factors, and neurotrophic factors have been found involved in adult neural precursors-niche interaction[6]. Molecules or pathways regulate niche factors required for the proliferation of neural precursor cells in adult brain are largely unknown. Β -arrestins (β -arrs), consisting of β -arr[1] and β -arr[2], are key regulators and mediators of G-protein coupled signaling processes. Both β -arr subtypes are expressed in many brain areas, including hippocampus[12]. We further propose that β -arr1-mediated signaling in niche astrocytes enhances the mitotic expansion of neural precursors in adult hippocampus and this may involve nuclear β -arr1-mediated transcription of excretive niche factors, such as BMP2, from astrocytes in neurogenic niche
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
