Abstract
N-myc downstream-regulated gene 2 (Ndrg2) is well-known for its involvement in tumor cell proliferation and differentiation. This promotes us to investigate whether Ndrg2 also functions in neurogenesis, during which some cellular events are similar to that of tumorigenesis. As the first step in exploring the role of Ndrg2 in neurogenesis, here we performed in situ hybridization with a Ndrg2-specific probe to examine Ndrg2 mRNA expression in neurogenic germinal zones of embryonic and postnatal mouse brain. Our results showed that Ndrg2 mRNA was highly expressed in the cortical ventricular zone at various embryonic stages. At postnatal stages, Ndrg2 transcripts were downregulated but still abundant in the subventricular zone of lateral ventricle and subgranular zone of hippocampal dentate gyrus where persistent neurogenesis occurs in the mammalian brain throughout life. Double staining of Ndrg2 mRNA with proliferation markers BrdU and Ki67, or with neural progenitor cell marker Nestin revealed that Ndrg2 was expressed in proliferating precursor cells. Thus, abundant expression of Ndrg2 mRNA in neural proliferating cell populations indicates an important role of Ndrg2 in neurogenesis of both embryonic and postnatal mouse brain.
Similar content being viewed by others
References
Deng YC, Yao LB, Liu XP, Nie XY, Wang JC, Zhang XG, Su CZ (2001) Exploring a new gene containing ACP like domain in human brain and expression of it in E. coli. Prog Biochem Biophys 28:72–76. doi:1000-3282.0.2001-01-019
Deng Y, Yao L, Chau L, Ng SS, Peng Y, Liu X, Au WS, Wang J, Li F, Ji S, Han H, Nie X, Li Q, Kung HF, Leung SY, Lin MC (2003) N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer 106(3):342–347. doi:10.1002/ijc.11228
Furuta H, Kondo Y, Nakahata S, Hamasaki M, Sakoda S, Morishita K (2010) NDRG2 is a candidate tumor-suppressor for oral squamous-cell carcinoma. Biochem Biophys Res Commun 391(4):1785–1791. doi:10.1016/j.bbrc.2009.12.156
Hu XL, Liu XP, Deng YC, Lin SX, Wu L, Zhang J, Wang LF, Wang XB, Li X, Shen L, Zhang YQ, Yao LB (2006) Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues. Cell Tissue Res 325(1):67–76. doi:10.1007/s00441-005-0137-5
Hwang J, Kim Y, Kang HB, Jaroszewski L, Deacon AM, Lee H, Choi WC, Kim KJ, Kim CH, Kang BS, Lee JO, Oh TK, Kim JW, Wilson IA, Kim MH (2011) Crystal structure of the human N-Myc downstream-regulated gene 2 protein provides insight into its role as a tumor suppressor. J Biol Chem 286(14):12450–12460. doi:10.1074/jbc.M110.170803
Kim YJ, Yoon SY, Kim JT, Song EY, Lee HG, Son HJ, Kim SY, Cho D, Choi I, Kim JH, Kim JW (2009) NDRG2 expression decreases with tumor stages and regulates TCF/beta-catenin signaling in human colon carcinoma. Carcinogenesis 30(4):598–605. doi:10.1093/carcin/bgp047
Li Y, Shen L, Cai L, Wang Q, Hou W, Wang F, Zeng Y, Zhao G, Yao L, Xiong L (2011) Spatial-temporal expression of NDRG2 in rat brain after focal cerebral ischemia and reperfusion. Brain Res 1382:252–258. doi:10.1016/j.brainres.2011.01.023
Liu Y, Yang FC, Okuda T, Dong X, Zylka MJ, Chen CL, Anderson DJ, Kuner R, Ma Q (2008) Mechanisms of compartmentalized expression of Mrg class G-protein-coupled sensory receptors. J Neurosci 28(1):125–132. doi:10.1523/j.neurosci.4472-07.2008
Liu Y, Abdel Samad O, Zhang L, Duan B, Tong Q, Lopes C, Ji RR, Lowell BB, Ma Q (2010) VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron 68(3):543–556. doi:10.1016/j.neuron.2010.09.008
Mitchelmore C, Buchmann-Moller S, Rask L, West MJ, Troncoso JC, Jensen NA (2004) NDRG2: a novel Alzheimer’s disease associated protein. Neurobiol Dis 16(1):48–58. doi:10.1016/j.nbd.2004.01.003
Mu Y, Lee SW, Gage FH (2010) Signaling in adult neurogenesis. Curr Opin Neurobiol 20(4):416–423. doi:10.1016/j.conb.2010.04.010
Nichols NR (2003) Ndrg2, a novel gene regulated by adrenal steroids and antidepressants, is highly expressed in astrocytes. Ann NY Acad Sci 1007:349–356. doi:10.1196/annals.1286.034
Nichols NR, Agolley D, Zieba M, Bye N (2005) Glucocorticoid regulation of glial responses during hippocampal neurodegeneration and regeneration. Brain Res Brain Res Rev 48(2):287–301. doi:10.1016/j.brainresrev.2004.12.019
Okuda T, Kondoh H (1999) Identification of new genes ndr2 and ndr3 which are related to Ndr1/RTP/Drg1 but show distinct tissue specificity and response to N-myc. Biochem Biophys Res Commun 266(1):208–215. doi:10.1006/bbrc.1999.1780
Okuda T, Kokame K, Miyata T (2008) Differential expression patterns of NDRG family proteins in the central nervous system. J Histochem Cytochem 56(2):175–182. doi:10.1369/jhc.7A7323.2007
Shen L, Zhao ZY, Wang YZ, Ji SP, Liu XP, Liu XW, Che HL, Lin W, Li X, Zhang J, Yao LB (2008) Immunohistochemical detection of Ndrg2 in the mouse nervous system. Neuroreport 19(9):927–931. doi:10.1097/WNR.0b013e32830163d0
Shi M, Guo C, Dai JX, Ding YQ (2008) DCC is required for the tangential migration of noradrenergic neurons in locus coeruleus of mouse brain. Mol Cell Neurosci 39(4):529–538. doi:10.1016/j.mcn.2008.07.023
Shi H, Jin H, Chu D, Wang W, Zhang J, Chen C, Xu C, Fan D, Yao L (2009) Suppression of N-myc downstream-regulated gene 2 is associated with induction of Myc in colorectal cancer and correlates closely with differentiation. Biol Pharm Bull 32(6):968–975. doi:JST.JSTAGE/bpb/32.968
Suh H, Deng W, Gage FH (2009) Signaling in adult neurogenesis. Annu Rev Cell Dev Biol 25:253–275. doi:10.1146/annurev.cellbio.042308.113256
Takahashi K, Yamada M, Ohata H, Honda K (2005) Ndrg2 promotes neurite outgrowth of NGF-differentiated PC12 cells. Neurosci Lett 388(3):157–162. doi:10.1016/j.neulet.2005.06.055
Takeichi T, Takarada-Iemata M, Hashida K, Sudo H, Okuda T, Kokame K, Hatano T, Takanashi M, Funabe S, Hattori N, Kitamura O, Kitao Y, Hori O (2011) The effect of Ndrg2 expression on astroglial activation. Neurochem Int 59(1):21–27. doi:10.1016/j.neuint.2011.03.019
Wang L, Liu N, Yao L, Li F, Zhang J, Deng Y, Liu J, Ji S, Yang A, Han H, Zhang Y, Han W, Liu X (2008) NDRG2 is a new HIF-1 target gene necessary for hypoxia-induced apoptosis in A549 cells. Cell Physiol Biochem 21(1–3):239–250. doi:10.1159/000113765
Yao L, Zhang J, Liu X (2008) NDRG2: a Myc-repressed gene involved in cancer and cell stress. Acta Biochim Biophys Sin (Shanghai) 40(7):625–635. doi:10.1111/j.1745-7270.2008.00434.x
Zhang J, Li F, Liu X, Shen L, Liu J, Su J, Zhang W, Deng Y, Wang L, Liu N, Han W, Ji S, Yang A, Han H, Yao L (2006) The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter. J Biol Chem 281(51):39159–39168. doi:10.1074/jbc.M605820200
Zhang J, Liu J, Li X, Li F, Wang L, Liu X, Shen L, Liu N, Deng Y, Yang A, Han H, Zhao M, Yao L (2007) The physical and functional interaction of NDRG2 with MSP58 in cells. Biochem Biophys Res Commun 352(1):6–11. doi:10.1016/j.bbrc.2006.10.141
Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (No. 30772516 and No. 31170801).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Lijuan Liu and Ming Shi contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
10735_2011_9378_MOESM1_ESM.tif
Supplemental Fig. 1. Co-expression of Ndrg2 and GFAP in the SVZ and SGZ. Ndrg2-expressing cells were GFAP-positive in the SVZ (A-D, D’, arrows in A) and SGZ (E–H, H’). Ndrg2 in situ hybridization signals in bright field images (A, E) were pseudo-colored green (B, F). Insets (D’) and (H’) show high magnification view of the regions outlined by the boxes in panels (D) and (H), respectively. Arrows in panels (D’, H’) refer to Ndrg2/GFAP double-labeled cells. Scale bars: 200 μm (A-D), 100 μm (E–H), 50 μm (D’), 25 μm (H’). cc, corpus callosum; Hil, hilus; LV, lateral ventricle; Str, striatum. (TIFF 3859 kb)
Rights and permissions
About this article
Cite this article
Liu, L., Shi, M., Wang, L. et al. Ndrg2 expression in neurogenic germinal zones of embryonic and postnatal mouse brain. J Mol Hist 43, 27–35 (2012). https://doi.org/10.1007/s10735-011-9378-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-011-9378-7