BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

ErbB3 binding protein 1 contributes to adult hippocampal neurogenesis by modulating Bmp4 and Ascl1 signaling

  • Youngkwan Kim (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Hyo Rim Ko (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Inwoo Hwang (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine) ;
  • Jee-Yin Ahn (Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine)
  • Received : 2023.08.21
  • Accepted : 2023.09.28
  • Published : 2024.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Neural stem cells (NSCs) in the adult hippocampus divide infrequently; the endogenous molecules modulating adult hippocampal neurogenesis (AHN) remain largely unknown. Here, we show that ErbB3 binding protein 1 (Ebp1), which plays important roles in embryonic neurodevelopment, acts as an essential modulator of adult neurogenic factors. In vivo analysis of Ebp1 neuron depletion mice showed impaired AHN with a low number of hippocampal NSCs and neuroblasts. Ebp1 leads to transcriptional repression of Bmp4 and suppression of Ascl1 promoter methylation in the dentate gyrus of the adult hippocampus reflecting an unusually high level of Bmp4 and low Ascl1 level in neurons of Ebp1-deficient mice. Therefore, our findings suggests that Ebp1 could act as an endogenous modulator of the interplay between Bmp4 and Ascl1/Notch signaling, contributing to AHN.

Keywords

Acknowledgement

This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute and Korea Dementia Research Center, funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (grant number: HU21C0157) to J-Y. Ahn.

References

  1. Spalding KL, Bergmann O, Alkass K et al (2013) Dynamics of hippocampal neurogenesis in adult humans. Cell 153, 1219-1227  https://doi.org/10.1016/j.cell.2013.05.002
  2. Ferri AL, Cavallaro M, Braida D et al (2004) Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131, 3805-3819  https://doi.org/10.1242/dev.01204
  3. Hattiangady B and Shetty AK (2008) Aging does not alter the number or phenotype of putative stem/progenitor cells in the neurogenic region of the hippocampus. Neurobiol Aging 29, 129-147  https://doi.org/10.1016/j.neurobiolaging.2006.09.015
  4. Varga AC and Wrana JL (2005) The disparate role of BMP in stem cell biology. Oncogene 24, 5713-5721  https://doi.org/10.1038/sj.onc.1208919
  5. Morrison SJ and Spradling AC (2008) Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell 132, 598-611  https://doi.org/10.1016/j.cell.2008.01.038
  6. Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM and Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28, 713-726  https://doi.org/10.1016/S0896-6273(00)00148-3
  7. Coskun V, Venkatraman G, Yang H, Rao MS and Luskin MB (2001) Retroviral manipulation of the expression of bone morphogenetic protein receptor Ia by SVZa progenitor cells leads to changes in their p19(INK4d) expression but not in their neuronal commitment. Int J Dev Neurosci 19, 219-227  https://doi.org/10.1016/S0736-5748(00)00092-7
  8. Colak D, Mori T, Brill MS et al (2008) Adult neurogenesis requires Smad4-mediated bone morphogenic protein signaling in stem cells. J Neurosci 28, 434-446  https://doi.org/10.1523/JNEUROSCI.4374-07.2008
  9. Bonaguidi MA, Peng CY, McGuire T et al (2008) Noggin expands neural stem cells in the adult hippocampus. J Neurosci 28, 9194-9204  https://doi.org/10.1523/JNEUROSCI.3314-07.2008
  10. Mira H, Andreu Z, Suh H et al (2010) Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus. Cell Stem Cell 7, 78-89  https://doi.org/10.1016/j.stem.2010.04.016
  11. Bertrand N, Castro DS and Guillemot F (2002) Proneural genes and the specification of neural cell types. Nat Rev Neurosci 3, 517-530  https://doi.org/10.1038/nrn874
  12. Vierbuchen T, Ostermeier A, Pang ZP, Kokubu Y, Sudhof TC and Wernig M (2010) Direct conversion of fibroblasts to functional neurons by defined factors. Nature 463, 1035-1041  https://doi.org/10.1038/nature08797
  13. Kim EJ, Ables JL, Dickel LK, Eisch AJ and Johnson JE (2011) Ascl1 (Mash1) defines cells with long-term neurogenic potential in subgranular and subventricular zones in adult mouse brain. PLoS One 6, e18472 
  14. Demars MP, Hollands C, Zhao Kda T and Lazarov O (2013) Soluble amyloid precursor protein-alpha rescues age-linked decline in neural progenitor cell proliferation. Neurobiol Aging 34, 2431-2440  https://doi.org/10.1016/j.neurobiolaging.2013.04.016
  15. Bergmann O, Spalding KL and Frisen J (2015) Adult neurogenesis in humans. Cold Spring Harb Perspect Biol 7, a018994 
  16. Kempermann G, Gage FH, Aigner L et al (2018) Human adult neurogenesis: evidence and remaining questions. Cell Stem Cell 23, 25-30  https://doi.org/10.1016/j.stem.2018.04.004
  17. Hwang I, Ko HR and Ahn JY (2020) The roles of multifunctional protein ErbB3 binding protein 1 (EBP1) isoforms from development to disease. Exp Mol Med 52, 1039-1047  https://doi.org/10.1038/s12276-020-0476-z
  18. Ko HR, Hwang I, Ahn SY, Chang YS, Park WS and Ahn JY (2017) Neuron-specific expression of p48 Ebp1 during murine brain development and its contribution to CNS axon regeneration. BMB Rep 50, 126-131  https://doi.org/10.5483/BMBRep.2017.50.3.190
  19. Masaki H, Nishida T, Sakasai R and Teraoka H (2010) DPPA4 modulates chromatin structure via association with DNA and core histone H3 in mouse embryonic stem cells. Genes Cells 15, 327-337  https://doi.org/10.1111/j.1365-2443.2010.01382.x
  20. Somanath P, Bush KM and Knoepfler PS (2018) ERBB3-binding protein 1 (EBP1) is a novel developmental pluripotency-associated-4 (DPPA4) cofactor in human pluripotent cells. Stem Cells 36, 671-682  https://doi.org/10.1002/stem.2776
  21. Kraushar ML, Krupp F, Harnett D et al (2021) Protein synthesis in the developing neocortex at near-atomic resolution reveals Ebp1-mediated neuronal proteostasis at the 60S tunnel exit. Mol Cell 81, 304-322 e316 
  22. Ko HR, Hwang I, Jin EJ et al (2019) Roles of ErbB3-binding protein 1 (EBP1) in embryonic development and gene-silencing control. Proc Natl Acad Sci U S A 116, 24852-24860  https://doi.org/10.1073/pnas.1916306116
  23. Kim BS, Ko HR, Hwang I, Cho SW and Ahn JY (2021) EBP1 regulates Suv39H1 stability via the ubiquitin-proteasome system in neural development. BMB Rep 54, 413-418  https://doi.org/10.5483/BMBRep.2021.54.8.022
  24. Hwang I, Kim BS, Ko HR et al (2022) Cerebellar dysfunction and schizophrenia-like behavior in Ebp1-deficient mice. Mol Psychiatry 27, 2030-2041  https://doi.org/10.1038/s41380-022-01458-1
  25. Moreno-Jimenez EP, Flor-Garcia M, Terreros-Roncal J et al (2019) Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer's disease. Nat Med 25, 554-560  https://doi.org/10.1038/s41591-019-0375-9
  26. Miller FD and Gauthier-Fisher A (2009) Home at last: neural stem cell niches defined. Cell Stem Cell 4, 507-510  https://doi.org/10.1016/j.stem.2009.05.008
  27. Voog J and Jones DL (2010) Stem cells and the niche: a dynamic duo. Cell Stem Cell 6, 103-115  https://doi.org/10.1016/j.stem.2010.01.011
  28. Castro DS, Martynoga B, Parras C et al (2011) A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets. Genes Dev 25, 930-945  https://doi.org/10.1101/gad.627811
  29. Park NI, Guilhamon P, Desai K et al (2017) ASCL1 Reorganizes chromatin to direct neuronal fate and suppress tumorigenicity of glioblastoma stem cells. Cell Stem Cell 21, 209-224 e207 
  30. Li L and Clevers H (2010) Coexistence of quiescent and active adult stem cells in mammals. Science 327, 542-545  https://doi.org/10.1126/science.1180794
  31. Xu H, Huang W, Wang Y et al (2013) The function of BMP4 during neurogenesis in the adult hippocampus in Alzheimer's disease. Ageing Res Rev 12, 157-164  https://doi.org/10.1016/j.arr.2012.05.002
  32. Nakatsu D, Kunishige R, Taguchi Y et al (2023) BMP4-SMAD1/5/9-RUNX2 pathway activation inhibits neurogenesis and oligodendrogenesis in Alzheimer's patients' iPSCs in senescence-related conditions. Stem Cell Reports 18, 688-705 https://doi.org/10.1016/j.stemcr.2023.01.004