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Sox2 in the adult rat sensory nervous system

An Erratum to this article was published on 06 March 2014

Abstract

Sex-determining region Y (SRY)-box 2 (Sox2) is a member of the Sox family transcription factors. In the central nervous system, Sox2 is expressed in neural stem cells from neurogenic regions, and regulates stem cell proliferation and differentiation. In the peripheral nervous system, Sox2 is found only in the immature and dedifferentiated Schwann cells, and is involved in myelination inhibition or N-cadherin redistribution. In the present immunohistochemical study, we found that Sox2 is also expressed in other cells of the adult rat peripheral nervous system. Nuclear Sox2 was observed in all satellite glial cells, non-myelinating Schwann cells, and the majority of terminal Schwann cells that form lamellar corpuscles and longitudinal lanceolate endings. Sox2 was not found in myelinating Schwann cells and terminal Schwann cells of subepidermal free nerve endings. Satellite glial cells exhibit strong Sox2 immunoreactivity, whereas non-myelinating Schwann cells show weak immunoreactivity. RT-PCR confirmed the presence of Sox2 mRNA, indicating that the cells are likely Sox2 expressors. Our findings suggest that the role of Sox2 in the peripheral nervous system may be cell-type-dependent.

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References

  • Aquino JB, Hjerling-Leffler J, Koltzenburg M, Edlund T, Villar MJ, Ernfors P (2006) In vitro and in vivo differentiation of boundary cap neural crest stem cells into mature Schwann cells. Exp Neurol 198:438–449

    CAS  PubMed  Article  Google Scholar 

  • Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R (2003) Multipotent cell lineages in early mouse development depend on Sox2 function. Genes Dev 17:126–140

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Bani-Yaghoub M, Tremblay RG, Lei JX, Zhang D, Zurakowski B, Sandhu JK, Smith B, Ribecco-Lutkiewicz M, Kennedy J, Walker PR, Sikorska M (2006) Role of Sox2 in the development of the mouse neocortex. Dev Biol 295:52–66

    CAS  PubMed  Article  Google Scholar 

  • Bass AJ, Watanabe H, Mermel CH, Yu S, Perner S, Verhaak RG, Kim SY, Wardwell L, Tamayo P, Gat-Viks I, Ramos AH, Woo MS, Weir BA, Getz G, Beroukhim R, O’Kelly M, Dutt A, Rozenblatt-Rosen O, Dziunycz P, Komisarof J, Chirieac LR, Lafargue CJ, Scheble V, Wilbertz T, Ma C, Rao S, Nakagawa H, Stairs DB, Lin L, Giordano TJ, Wagner P, Minna JD, Gazdar AF, Zhu CQ, Brose MS, Cecconello I, Ribeiro U Jr, Marie SK, Dahl O, Shivdasani RA, Tsao MS, Rubin MA, Wong KK, Regev A, Hahn WC, Beer DG, Rustgi AK, Meyerson M (2009) SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet 41:1238–1242

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Biernaskie J, Paris M, Morozova O, Fagan BM, Marra M, Pevny L, Miller FD (2009) SKPs derive from hair follicle precursors and exhibit properties of adult dermal stem cells. Cell Stem Cell 5:610–623

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Cauna N (1969) The fine morphology of the sensory receptor organs in the auricle of the rat. J Comp Neurol 136:81–98

    CAS  PubMed  Article  Google Scholar 

  • Cauna N (1973) The free penicillate nerve endings of the human hairy skin. J Anat 115:277–288

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cavallaro M, Mariani J, Lancini C, Latorre E, Caccia R, Gullo F, Valotta M, DeBiasi S, Spinardi L, Ronchi A, Wanke E, Brunelli S, Favaro R, Ottolenghi S, Nicolis SK (2008) Impaired generation of mature neurons by neural stem cells from hypomorphic Sox2 mutants. Development 135(3):541–557

    CAS  PubMed  Article  Google Scholar 

  • Ciaroni S, Cecchini T, Cuppini R, Ferri P, Ambrogini P, Bruno C, Del Grande P (2000) Are there proliferating neuronal precursors in adult rat dorsal root ganglia? Neurosci Lett 281:69–71

    CAS  PubMed  Article  Google Scholar 

  • Cimadamore F, Fishwick K, Giusto E, Gnedeva K, Cattarossi G, Miller A, Pluchino S, Brill LM, Bronner-Fraser M, Terskikh AV (2011) Human ESC-derived neural crest model reveals a key role for Sox2 in sensory neurogenesis. Cell Stem Cell 8:538–551

    CAS  PubMed  Article  Google Scholar 

  • Driskell RR, Giangreco A, Jensen KB, Mulder KW, Watt FM (2009) Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis. Development 136:2815–2823

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Farel PB (2002) Sensory neuron addition in juvenile rat: time course and specificity. J Comp Neurol 449:158–165

    PubMed  Article  Google Scholar 

  • Farel PB (2003) Late differentiation contributes to the apparent increase in sensory neuron number in juvenile rat. Brain Res Dev Brain Res 144:91–98

    CAS  PubMed  Article  Google Scholar 

  • Favaro R, Valotta M, Ferri AL, Latorre E, Mariani J, Giachino C, Lancini C, Tosetti V, Ottolenghi S, Taylor V, Nicolis SK (2009) Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci 12:1248–1256

    CAS  PubMed  Article  Google Scholar 

  • Ferri AL, Cavallaro M, Braida D, Di Cristofano A, Canta A, Vezzani A, Ottolenghi S, Pandolfi PP, Sala M, DeBiasi S, Nicolis SK (2004) Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development 131:3805–3819

    CAS  PubMed  Article  Google Scholar 

  • Graham V, Khudyakov J, Ellis P, Pevny L (2003) Sox2 functions to maintain neural progenitor identity. Neuron 39:749–765

    CAS  PubMed  Article  Google Scholar 

  • Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Munsterberg A, Vivian N, Goodfellow P, Lovell-Badge R (1990) A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature 346:245–250

    CAS  PubMed  Article  Google Scholar 

  • Hanani M (2005) Satellite glial cells in sensory ganglia: from form to function. Brain Res Brain Res Rev 48:457–476

    CAS  PubMed  Article  Google Scholar 

  • Heanue TA, Pachnis V (2011) Prospective identification and isolation of enteric nervous system progenitors using Sox2. Stem Cells 29:128–140

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Ikushima H, Todo T, Ino Y, Takahashi M, Miyazawa K, Miyazono K (2009) Autocrine TGF-beta signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors. Cell Stem Cell 5:504–514

    CAS  PubMed  Article  Google Scholar 

  • Jessen KR, Mirsky R (2005) The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci 6:671–682

    CAS  PubMed  Article  Google Scholar 

  • Jirmanova I, Dubovy P, Zelena J (1997) Regeneration of tactile lamellar corpuscles of the rat after postnatal freeze injury. Anat Embryol (Berl) 195:363–374

    CAS  Article  Google Scholar 

  • Kruger L, Perl ER, Sedivec MJ (1981) Fine structure of myelinated mechanical nociceptor endings in cat hairy skin. J Comp Neurol 198:137–154

    CAS  PubMed  Article  Google Scholar 

  • La Forte RA, Melville S, Chung K, Coggeshall RE (1991) Absence of neurogenesis of adult rat dorsal root ganglion cells. Somatosens Mot Res 8:3–7

    PubMed  Article  Google Scholar 

  • Laga AC, Lai CY, Zhan Q, Huang SJ, Velazquez EF, Yang Q, Hsu MY, Murphy GF (2010) Expression of the embryonic stem cell transcription factor Sox2 in human skin: relevance to melanocyte and merkel cell biology. Am J Pathol 176:903–913

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Le N, Nagarajan R, Wang JY, Araki T, Schmidt RE, Milbrandt J (2005) Analysis of congenital hypomyelinating Egr2Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination. Proc Natl Acad Sci USA 102:2596–2601

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Li HY, Say EH, Zhou XF (2007) Isolation and characterization of neural crest progenitors from adult dorsal root ganglia. Stem Cells 25:2053–2065

    CAS  PubMed  Article  Google Scholar 

  • Liu Z, Walters BJ, Owen T, Brimble MA, Steigelman KA, Zhang L, Mellado Lagarde MM, Valentine MB, Yu Y, Cox BC, Zuo J (2012) Regulation of p27Kip1 by Sox2 maintains quiescence of inner pillar cells in the murine auditory sensory epithelium. J Neurosci 32:10530–10540

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Miller R (2004) Schwann cell development. In: Lazzarini RA (ed) Myelin Biology and Disorders 1, 2nd edn. Elsevier, USA, pp 329–370

    Google Scholar 

  • Miller KE, Richards BA, Kriebel RM (2002) Glutamine-, glutamine synthetase-, glutamate dehydrogenase- and pyruvate carboxylase-immunoreactivities in the rat dorsal root ganglion and peripheral nerve. Brain Res 945:202–211

    CAS  PubMed  Article  Google Scholar 

  • Munger BL, Halata Z (1983) The sensory innervation of primate facial skin. I. Hairy skin. Brain Res 286:45–80

    CAS  Google Scholar 

  • Namaka MP, Sawchuk M, MacDonald SC, Jordan LM, Hochman S (2001) Neurogenesis in postnatal mouse dorsal root ganglia. Exp Neurol 172:60–69

    CAS  PubMed  Article  Google Scholar 

  • Pannese E (1960) Observations on the morphology, submicroscopic structure and biological properties of satellite cells (s.c.) in sensory ganglia of mammals. Z Zellforsch Mikrosk Anat 52:567–597

    CAS  PubMed  Article  Google Scholar 

  • Parkinson DB, Bhaskaran A, Arthur-Farraj P, Noon LA, Woodhoo A, Lloyd AC, Feltri ML, Wrabetz L, Behrens A, Mirsky R, Jessen KR (2008) c-Jun is a negative regulator of myelination. J Cell Biol 181(4):625–634

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Parrinello S, Napoli I, Ribeiro S, Digby PW, Fedorova M, Parkinson DB, Doddrell RD, Nakayama M, Adams RH, Lloyd AC (2010) EphB signaling directs peripheral nerve regeneration through Sox2-dependent Schwann cell sorting. Cell 143:145–155

    CAS  PubMed  Article  Google Scholar 

  • Popken GJ, Farel PB (1997) Sensory neuron number in neonatal and adult rats estimated by means of stereologic and profile-based methods. J Comp Neurol 386:8–15

    CAS  PubMed  Article  Google Scholar 

  • Pover CM, Barnes MC, Coggeshall RE (1994) Do primary afferent cell numbers change in relation to increasing weight and surface area in adult rats? Somatosense Mot Res 11:163–167

    CAS  Article  Google Scholar 

  • Sarkar A, Hochedlinger K (2013) The sox family of transcription factors: versatile regulators of stem and progenitor cell fate. Cell Stem Cell 12:15–30

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  • Su PH, Chen CC, Chang YF, Wong ZR, Chang KW, Huang BM, Yang HY (2013) Identification and cytoprotective function of a novel nestin isoform, Nes-S, in dorsal root ganglia neurons. J Biol Chem 288:8391–8404

    CAS  PubMed  Article  Google Scholar 

  • Suh H, Consiglio A, Ray J, Sawai T, D'Amour KA, Gage FH (2007) In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. Cell Stem Cell 1:515–528

    Google Scholar 

  • Wakamatsu Y, Maynard TM, Weston JA (2000) Fate determination of neural crest cells by NOTCH-mediated lateral inhibition and asymmetrical cell division during gangliogenesis. Development 127:2811–2821

    CAS  PubMed  Google Scholar 

  • Wakamatsu Y, Endo Y, Osumi N, Weston JA (2004) Multiple roles of Sox2, an HMG-box transcription factor in avian neural crest development. Dev Dyn 229:74–86

    CAS  PubMed  Article  Google Scholar 

  • Woodham P, Anderson PN, Nadim W, Turmaine M (1989) Satellite cells surrounding axotomised rat dorsal root ganglion cells increase expression of a GFAP-like protein. Neurosci Lett 98:8–12

    CAS  PubMed  Article  Google Scholar 

  • Zappone MV, Galli R, Catena R, Meani N, De Biasi S, Mattei E, Tiveron C, Vescovi AL, Lovell-Badge R, Ottolenghi S, Nicolis SK (2000) Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. Development 127:2367–2382

    CAS  PubMed  Google Scholar 

  • Zorick TS, Syroid DE, Arroyo E, Scherer SS, Lemke G (1996) The transcription factors SCIP and Krox-20 mark distinct stages and cell fates in Schwann cell differentiation. Mol Cell Neurosci 8:129–145

    CAS  Article  Google Scholar 

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Acknowledgments

This study was supported by a Grant D2 from Kansai Medical University (T.K.) and a Grant-in-Aid for Scientific Research C (No. 24500876) from the Japan Society for Promotion of Science (H.Y.).

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Correspondence to Hisao Yamada.

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Kioke, T., Wakabayashi, T., Mori, T. et al. Sox2 in the adult rat sensory nervous system. Histochem Cell Biol 141, 301–309 (2014). https://doi.org/10.1007/s00418-013-1158-x

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Keywords

  • Sox2
  • Peripheral nervous system
  • Satellite glial cell
  • Schwann cell
  • Immunohistochemistry
  • Rat