FOXG1 Contributes Adult Hippocampal Neurogenesis in Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.1.1. Foxg1 Transgenic Mice
2.1.2. Forced Expression of FOXG1 in Adult Hippocampal DG of the Foxg1fl/fl Mice
2.2. Histology
2.3. Western Blot Analysis
2.4. Immunohistochemistry
2.5. Immunofluorescence
2.6. Cell Cycle Analysis
2.6.1. Establishment and Evaluation of FUCCI System
2.6.2. One-Dimensional DNA Measurement of G1-Phase Exit
2.6.3. Two-Dimensional DNA and RNA Analyses of Cell Cycle Redistribution
2.6.4. Flow Cytometry Detection of p21 Expression
2.7. Hippocapal aNSC Cultures
2.7.1. Sample Harvesting
2.7.2. Preparation of Single Cell Suspension and Cell Inoculation
2.7.3. Morphological Observation
2.8. Statistical Analyses
3. Results
3.1. FOXG1 Is Forced Overexpressing in the Hippocampal DG of the Foxg1fl/fl Mouse by Infusing CreAAV
3.2. FOXG1 Enlarges aNSC Pool and Promotes Their Activation in the Hippocampal DG of Foxg1 Genotype Mice
3.3. FOXG1 Promotes the Formation of Neurosphere and Suppresses p21cip1-Mediated Cell Cycle Exit
3.4. FOXG1 Induces aNSCs Giving Rise to Intermediate Progenitor Cells (IPCs) and Enlarges IPC Pool during Precursor Cell Stage
3.5. FOXG1 Induces Amplifying Progenitors Giving Rise to Newborn Neuroblasts during Precursor Cell Stage
3.6. FOXG1 Affects Cell-Cycle Redistribution
3.7. FOXG1 Promotes Rise of the Final Mature Granule Neurons and Contributes to Synaptic Plasticity during Postmitotic Maturation Phase
3.8. FOXG1 Can’t Induce the Production of Oligodendrocytes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Kitamura, T.; Saitoh, Y.; Takashima, N.; Murayama, A.; Niibori, Y.; Ageta, H.; Sekiguchi, M.; Sugiyama, H.; Inokuchi, K. Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell 2009, 139, 814–827. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Squire, L.R. Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans. Psychol. Rev. 1992, 99, 195–231. [Google Scholar] [CrossRef] [PubMed]
- Matsuzaki, M.; Honkura, N.; Ellis-Davies, G.C.; Kasai, H. Structural basis of long-term potentiation in single dendritic spines. Nature 2004, 429, 761–766. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sahay, A.; Scobie, K.N.; Hill, A.S.; O’Carroll, C.M.; Kheirbek, M.A.; Burghardt, N.S.; Fenton, A.A.; Dranovsky, A.; Hen, R. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 2011, 472, 466–470. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Siegenthaler, J.A.; Tremper-Wells, B.A.; Miller, M.W. Foxg1 haploinsufficiency reduces the population of cortical intermediate progenitor cells: Effect of increased p21 expression. Cereb. Cortex 2008, 18, 1865–1875. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vezzali, R.; Weise, S.C.; Hellbach, N.; Machado, V.; Heidrich, S.; Vogel, T. The FOXG1/FOXO/SMAD network balances proliferation and differentiation of cortical progenitors and activates Kcnh3 expression in mature neurons. Oncotarget 2016, 7, 37436–37455. [Google Scholar] [CrossRef] [Green Version]
- Hanashima, C.; Li, S.C.; Shen, L.; Lai, E.; Fishell, G. Foxg1 suppresses early cortical cell fate. Science 2004, 303, 56–59. [Google Scholar] [CrossRef] [Green Version]
- Chen, D.; Wang, C.; Li, M.; She, X.; Yuan, Y.; Chen, H.; Zhang, W.; Zhao, C. Loss of Foxg1 Impairs the Development of Cortical SST-Interneurons Leading to Abnormal Emotional and Social Behaviors. Cereb. Cortex 2019, 29, 3666–3682. [Google Scholar] [CrossRef]
- Fasano, C.A.; Phoenix, T.N.; Kokovay, E.; Lowry, N.; Elkabetz, Y.; Dimos, J.T.; Lemischka, I.R.; Studer, L.; Temple, S. Bmi-1 cooperates with Foxg1 to maintain neural stem cell self-renewal in the forebrain. Genes Dev. 2009, 23, 561–574. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Song, H.R.; Guo, M.N.; Ma, S.F.; Yun, Q.; Liu, W.J.; Hu, Y.M.; Zhu, Y.Q. PGC-1alpha regulate critical period plasticity via gene x environment interaction in the developmental trajectory to schizophrenia. Biochem. Biophys. Res. Commun. 2020, 525, 989–996. [Google Scholar] [CrossRef]
- Wang, J.; Yun, Q.; Qian, J.J.; Song, H.R.; Wang, L.; Inkabi, S.E.; Xu, R.J.; Hu, Y.M.; Zhang, W.N.; Einat, H. Mice Lacking the Transcriptional Coactivator PGC-1alpha Exhibit Hyperactivity. Neuropsychobiology 2019, 78, 182–188. [Google Scholar] [CrossRef] [PubMed]
- Liu, Z.; Wang, X.; Xing, Z.; Xu, P.; Sun, J. Nano-Cerium Oxide Promotes Proliferation of Hepatoma Cells and Regulates mRNA Expression of Apoptosis-Related Genes Bcl-2 and Bax, as Detected Through Real-Time Fluorescent Quantitative Polymerase Chain Reaction. J. Nanosci. Nanotechnol. 2020, 20, 7457–7463. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Song, H.R.; Guo, M.N.; Ma, S.F.; Yun, Q.; Zhang, W.N. Adult conditional knockout of PGC-1alpha in GABAergic neurons causes exaggerated startle reactivity, impaired short-term habituation and hyperactivity. Brain Res. Bull. 2020, 157, 128–139. [Google Scholar] [CrossRef] [PubMed]
- Shapiro, H.M. Flow cytometric estimation of DNA and RNA content in intact cells stained with Hoechst 33342 and pyronin Y. Cytometry 1981, 2, 143–150. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hu, Y.D.; Zhao, Q.; Zhang, X.R.; Xiong, L.L.; Zhang, Z.B.; Zhang, P.; Zhang, R.P.; Wang, T.H. Comparison of the properties of neural stem cells of the hippocampus in the tree shrew and rat in vitro. Mol. Med. Rep. 2018, 17, 5676–5683. [Google Scholar] [CrossRef] [Green Version]
- Kempermann, G.; Song, H.; Gage, F.H. Neurogenesis in the Adult Hippocampus. Cold Spring Harb. Perspect. Biol. 2015, 7, a018812. [Google Scholar] [CrossRef] [Green Version]
- Giachino, C.; Basak, O.; Lugert, S.; Knuckles, P.; Obernier, K.; Fiorelli, R.; Frank, S.; Raineteau, O.; Alvarez-Buylla, A.; Taylor, V. Molecular diversity subdivides the adult forebrain neural stem cell population. Stem Cells 2014, 32, 70–84. [Google Scholar] [CrossRef] [Green Version]
- Calder, A.; Roth-Albin, I.; Bhatia, S.; Pilquil, C.; Lee, J.H.; Bhatia, M.; Levadoux-Martin, M.; McNicol, J.; Russell, J.; Collins, T.; et al. Lengthened G1 phase indicates differentiation status in human embryonic stem cells. Stem Cells Dev. 2013, 22, 279–295. [Google Scholar] [CrossRef] [Green Version]
- Salomoni, P.; Calegari, F. Cell cycle control of mammalian neural stem cells: Putting a speed limit on G1. Trends Cell Biol. 2010, 20, 233–243. [Google Scholar] [CrossRef]
- Cucinotta, C.E.; Dell, R.H.; Braceros, K.C.; Tsukiyama, T. RSC primes the quiescent genome for hypertranscription upon cell-cycle re-entry. eLife 2021, 10, e67033. [Google Scholar] [CrossRef]
- Encinas, J.M.; Michurina, T.V.; Peunova, N.; Park, J.H.; Tordo, J.; Peterson, D.A.; Fishell, G.; Koulakov, A.; Enikolopov, G. Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell 2011, 8, 566–579. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Biswas, S.; Chung, S.H.; Jiang, P.; Dehghan, S.; Deng, W. Development of glial restricted human neural stem cells for oligodendrocyte differentiation in vitro and in vivo. Sci. Rep. 2019, 9, 9013. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Weise, S.C.; Arumugam, G.; Villarreal, A.; Videm, P.; Heidrich, S.; Nebel, N.; Dumit, V.I.; Sananbenesi, F.; Reimann, V.; Craske, M.; et al. FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus. Mol. Neurobiol. 2019, 56, 5188–5201. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schaffner, I.; Wittmann, M.T.; Vogel, T.; Lie, D.C. Differential vulnerability of adult neurogenic niches to dosage of the neurodevelopmental-disorder linked gene Foxg1. Mol. Psychiatry 2022, 56, 5188–5201. [Google Scholar] [CrossRef]
- Seri, B.; Garcia-Verdugo, J.M.; Collado-Morente, L.; McEwen, B.S.; Alvarez-Buylla, A. Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus. J. Comp. Neurol. 2004, 478, 359–378. [Google Scholar] [CrossRef]
- Tian, C.X.; Gong, Y.F.; Yang, Y.; Shen, W.; Wang, K.; Liu, J.H.; Xu, B.K.; Zhao, J.; Zhao, C.J. Foxg1 Has an Essential Role in Postnatal Development of the Dentate Gyrus. J. Neurosci. 2012, 32, 2931–2949. [Google Scholar] [CrossRef] [Green Version]
- Ming, G.L.; Song, H. Adult neurogenesis in the mammalian brain: Significant answers and significant questions. Neuron 2011, 70, 687–702. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Ma, S.F.; Yun, Q.; Liu, W.J.; Zhai, H.R.; Shi, H.Z.; Xie, L.G.; Qian, J.J.; Zhao, C.J.; Zhang, W.N. FOXG1 as a Potential Therapeutic Target for Alzheimer’s Disease with a Particular Focus on Cell Cycle Regulation. J. Alzheimers Dis. 2022, 86, 1255–1273. [Google Scholar] [CrossRef]
- Zhang, Z.; Ma, Z.; Zou, W.; Guo, H.; Liu, M.; Ma, Y.; Zhang, L. The Appropriate Marker for Astrocytes: Comparing the Distribution and Expression of Three Astrocytic Markers in Different Mouse Cerebral Regions. BioMed Res. Int. 2019, 2019, 9605265. [Google Scholar] [CrossRef]
- Merz, K.; Lie, D.C. Evidence that Doublecortin Is Dispensable for the Development of Adult Born Neurons in Mice. PLoS ONE 2013, 8, e62693. [Google Scholar] [CrossRef]
- Manuel, M.N.; Martynoga, B.; Molinek, M.D.; Quinn, J.C.; Kroemmer, C.; Mason, J.O.; Price, D.J. The transcription factor Foxg1 regulates telencephalic progenitor proliferation cell autonomously, in part by controlling Pax6 expression levels. Neural Dev. 2011, 6, 9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brancaccio, M.; Pivetta, C.; Granzotto, M.; Filippis, C.; Mallamaci, A. Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis. Stem Cells 2010, 28, 1206–1218. [Google Scholar] [CrossRef] [PubMed]
- Dong, F.; Liu, D.; Jiang, F.; Liu, Y.; Wu, X.; Qu, X.; Liu, J.; Chen, Y.; Fan, H.; Yao, R. Conditional Deletion of Foxg1 Alleviates Demyelination and Facilitates Remyelination via the Wnt Signaling Pathway in Cuprizone-Induced Demyelinated Mice. Neurosci. Bull. 2021, 37, 15–30. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Wang, J.; Zhai, H.-R.; Ma, S.-F.; Shi, H.-Z.; Zhang, W.-J.; Yun, Q.; Liu, W.-J.; Liu, Z.-Z.; Zhang, W.-N. FOXG1 Contributes Adult Hippocampal Neurogenesis in Mice. Int. J. Mol. Sci. 2022, 23, 14979. https://doi.org/10.3390/ijms232314979
Wang J, Zhai H-R, Ma S-F, Shi H-Z, Zhang W-J, Yun Q, Liu W-J, Liu Z-Z, Zhang W-N. FOXG1 Contributes Adult Hippocampal Neurogenesis in Mice. International Journal of Molecular Sciences. 2022; 23(23):14979. https://doi.org/10.3390/ijms232314979
Chicago/Turabian StyleWang, Jia, Hong-Ru Zhai, Si-Fei Ma, Hou-Zhen Shi, Wei-Jun Zhang, Qi Yun, Wen-Jun Liu, Zi-Zhong Liu, and Wei-Ning Zhang. 2022. "FOXG1 Contributes Adult Hippocampal Neurogenesis in Mice" International Journal of Molecular Sciences 23, no. 23: 14979. https://doi.org/10.3390/ijms232314979