Abstract
c-jun, a major component of AP-1 transcription factor, has a wide variety of functions. In the embryonic brain, c-jun mRNA is abundantly expressed in germinal layers around the ventricles. Although the subventricular zone (SVZ) of the adult brain is a derivative of embryonic germinal layers and contains neural precursor cells (NPCs), the c-jun expression pattern is not clear. To study the function of c-jun in adult neurogenesis, we analyzed c-jun expression in the adult SVZ by immunohistochemistry and compared it with that of the embryonic brain. We found that almost all proliferating embryonic NPCs expressed c-jun, but the number of c-jun immunopositive cells among proliferating adult NPCs was about half. In addition, c-jun was hardly expressed in post-mitotic migrating neurons in the embryonic brain, but the majority of c-jun immunopositive cells were tangentially migrating neuroblasts heading toward the olfactory bulb in the adult brain. In addition, status epilepticus is known to enhance the transient proliferation of adult NPCs, but the c-jun expression pattern was not significantly affected. These expression patterns suggest that c-jun has a pivotal role in the proliferation of embryonic NPCs, but it has also other roles in adult neurogenesis.
Similar content being viewed by others
References
Alfonso J, Penkert H, Duman C et al (2015) Downregulation of sphingosine 1-phosphate receptor 1 promotes the switch from tangential to radial migration in the OB. J Neurosci 35:13659–13672
Biebl M, Cooper CM, Winkler J, Kuhn HG (2000) Analysis of neurogenesis and programmed cell death reveals a self-renewing capacity in the adult rat brain. Neurosci Lett 291:17–20
Blau L, Knirsh R, Ben-Dror I et al (2012) Aberrant expression of c-Jun in glioblastoma by internal ribosome entry site (IRES)-mediated translational activation. Proc Natl Acad Sci U S A 109:E2875–E2884
Bolognani F, Perrone-Bizzozero NI (2008) RNA–protein interactions and control of mRNA stability in neurons. J Neurosci Res 86:481–489
Codega P, Silva-vargas V, Paul A et al (2014) Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron 82:545–559
Gleeson JG, Peter TL, Flanagan LA et al (1999) Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23:257–271
Herdegen T, Leah JD (1998) Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev 28:370–490
Herdegen T, Waetzig V (2001) AP-1 proteins in the adult brain: facts and fiction about effectors of neuroprotection and neurodegeneration. Oncogene 20:2424–2437
Jiao X, Katiyar S, Willmarth NE et al (2010) c-Jun induces mammary epithelial cellular invasion and breast cancer stem cell expansion. J Biol Chem 285:8218–8226
Kernie SG, Parent JM (2010) Forebrain neurogenesis after focal Ischemic and traumatic brain injury. Neurobiol Dis 37:267–274
Kimelberg HK (2004) The problem of astrocyte identity. Neurochem Int 45:191–202
Lalli G (2014) Extracellular signals controlling neuroblast migration in the postnatal brain. Adv Exp Med Biol 800:149–180
Lee W-CA, Huang H, Feng G et al (2006) Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex. PLoS Biol 4:e29
Lledo P-M, Saghatelyan A (2005) Integrating new neurons into the adult olfactory bulb: joining the network, life-death decisions, and the effects of sensory experience. Trends Neurosci 28:248–254
Lledo P, Alonso M, Grubb M (2006) Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci 7:179–193
Lu D-Y, Leung Y-M, Cheung C-W et al (2010) Glial cell line-derived neurotrophic factor induces cell migration and matrix metalloproteinase-13 expression in glioma cells. Biochem Pharmacol 80:1201–1209
Luhmann HJ, Fukuda A, Kilb W (2015) Control of cortical neuronal migration by glutamate and GABA. Front Cell Neurosci 9:4
Maslov AY, Barone TA, Plunkett RJ, Pruitt SC (2004) Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice. J Neurosci 24:1726–1733
Mazzitelli S, Xu P, Ferrer I et al (2011) The loss of c-Jun N-terminal protein kinase activity prevents the amyloidogenic cleavage of amyloid precursor protein and the formation of amyloid plaques in vivo. J Neurosci 31:16969–16976
Mellström B, Achaval M, Montero D et al (1991) Differential expression of the jun family members in rat brain. Oncogene 6:1959–1964
Merkle FT, Tramontin AD, García-Verdugo JM, Alvarez-Buylla A (2004) Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci U S A 101:17528–17532
Merkle FT, Mirzadeh Z, Alvarez-Buylla A (2007) Mosaic organization of neural stem cells in the adult brain. Science 317:381–384
Miyamoto A, Wake H, Ishikawa AW et al (2016) Microglia contact induces synapse formation in developing somatosensory cortex. Nat Commun 7:12540
Mori T, Buffo A, Götz M (2005) The novel roles of glial cells revisited: the contribution of radial glia and astrocytes to neurogenesis. Curr Top Dev Biol 69:67–99
Mori T, Wakabayashi T, Hirahara Y et al (2012) Differential responses of endogenous adult mouse neural precursors to excess neuronal excitation. Eur J Neurosci 36:3184–3193
Ouafik L, Berenguer-Daize C, Berthois Y (2009) Adrenomedullin promotes cell cycle transit and up-regulates cyclin D1 protein level in human glioblastoma cells through the activation of c-Jun/JNK/AP-1 signal transduction pathway. Cell Signal 21:597–608
Parent JM, Valentin VV, Lowenstein DH (2002) Prolonged seizures increase proliferating neuroblasts in the adult rat subventricular zone-olfactory bulb pathway. J Neurosci 22:3174–3188
Passegué E, Jochum W, Behrens A et al (2002) JunB can substitute for Jun in mouse development and cell proliferation. Nat Genet 30:158–166
Petreanu L, Alvarez-Buylla A (2002) Maturation and death of adult-born olfactory bulb granule neurons: role of olfaction. J Neurosci 22:6106–6113
Pinto JG, Jones DG, Murphy KM (2013) Comparing development of synaptic proteins in rat visual, somatosensory, and frontal cortex. Front Neural Circuits 7:97
Ponti G, Obernier K, Guinto C et al (2013) Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice. Proc Natl Acad Sci USA 110:E1045–E1054
Pramparo T, Youn YH, Yingling J et al (2010) Novel embryonic neuronal migration and proliferation defects in Dcx mutant mice are exacerbated by Lis1 reduction. J Neurosci 30:3002–3012
Raivich G, Behrens A (2006) Role of the AP-1 transcription factor c-Jun in developing, adult and injured brain. Prog Neurobiol 78:347–363
Raivich G, Bohatschek M, Da Costa C et al (2004) The AP-1 transcription factor c-Jun is required for efficient axonal regeneration. Neuron 43:57–67
Spassky N, Merkle FT, Flames N et al (2005) Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci 25:10–18
Takahashi T, Nowakowski RS, Caviness VS (1995) The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall. J Neurosci 15:6046–6057
Trachtenberg JT, Chen BE, Knott GW et al (2002) Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420:788–794
Wilkinson DG, Bhatt S, Ryseck RP, Bravo R (1989) Tissue-specific expression of c-jun and junB during organogenesis in the mouse. Development 106:465–471
Wilsch-Bräuninger M, Florio M, Huttner WB (2016) Neocortex expansion in development and evolution—from cell biology to single genes. Curr Opin Neurobiol 39:122–132
Zhang R, Zhang Z, Zhang C et al (2004) Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat. J Neurosci 24:5810–5815
Zhang RL, Zhang ZG, Roberts C et al (2008) Lengthening the G(1) phase of neural progenitor cells is concurrent with an increase of symmetric neuron generating division after stroke. J Cereb Blood Flow Metab 28:602–611
Acknowledgements
We thank Professor Dr. Masayoshi Okada for his critical review. This work was supported by JSPS KAKENHI Grant-in-Aid for Scientific Research(C), Grant Number: 25430044.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
This study was supported by JSPS KAKENHI Grant Number 25430044.
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
418_2016_1536_MOESM1_ESM.pptx
Online Resource 1 c-jun+ cells are not migrating cells of the embryonic brain. At E14, there is a scattering of c-jun+ cells lining the surface of the lateral ventricle that are DCX+ (arrows), and some of them are in telophase (double arrow). Single optical images of confocal microscopy are shown. Scale bar 12.5 μm. Online Resource 2 Status epilepticus enhances proliferation of adult NPCs. In the anterior part of the SVZ, a larger number of BrdU+ cells are detected in the SE group (b) than in the control group (a) 1 week after induction of SE. Light microscopy images are shown. (c) The number of BrdU+ cells is compared (n = 3). *, p<0.05. Scale bar 200 μm (PPTX 1052 KB)
Rights and permissions
About this article
Cite this article
Kawashima, F., Saito, K., Kurata, H. et al. c-jun is differentially expressed in embryonic and adult neural precursor cells. Histochem Cell Biol 147, 721–731 (2017). https://doi.org/10.1007/s00418-016-1536-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-016-1536-2