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Satb2-Independent Acquisition of the Cholinergic Sudomotor Phenotype in Rodents

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Abstract

Expression of Satb2 (Special AT-rich sequence-binding protein-2) elicits expression of the vesicular acetylcholine transporter (VAChT) and choline acetyltransferase (ChAT) in cultured rat sympathetic neurons exposed to soluble differentiation factors. Here, we determined whether or not Satb2 plays a similar role in cholinergic differentiation in vivo, by comparing the postnatal profile of Satb2 expression in the rodent stellate ganglion to that of VAChT and ChAT. Throughout postnatal development, VAChT and ChAT were found to be co-expressed in a numerically stable subpopulation of rat stellate ganglion neurons. Nerve fibers innervating rat forepaw sweat glands on P1 were VAChT immunoreactive, while ChAT was detectable at this target only after P5. The postnatal abundance of VAChT transcripts in the stellate ganglion was at maximum already on P1, whereas ChAT mRNA levels increased from low levels on P1 to reach maximum levels between P5 and P21. Satb2 mRNA was detected in cholinergic neurons in the stellate ganglion beginning with P8, thus coincident with the onset of unequivocal detection of ChAT immunoreactivity in forepaw sweat gland endings. Satb2 knockout mice exhibited no change in the P1 cholinergic VAChT/ChAT co-phenotype in stellate ganglion neurons. Thus, cholinergic phenotype maturation involves first, early target (sweat-gland)-independent expression and trafficking of VAChT, and later, potentially target- and Satb2-dependent elevation of ChAT mRNA and protein transport into sweat gland endings. In rat sudomotor neurons that, unlike mouse sudomotor neurons, co-express calcitonin gene-related peptide (CGRP), Satb2 may also be related to the establishment of species-specific neuropeptide co-phenotypes during postnatal development.

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References

  • Apostolova G, Loy B, Dorn R, Dechant G (2010) The sympathetic neurotransmitter switch depends on the nuclear matrix protein Satb2. J Neurosci 30(48):16356–16364

    Article  CAS  PubMed  Google Scholar 

  • Asmus SE, Parsons S, Landis SC (2000) Developmental changes in the transmitter properties of sympathetic neurons that innervate the periosteum. J Neurosci 20(4):1495–1504

    CAS  PubMed  Google Scholar 

  • Britanova O, de Juan RC, Cheung A, Kwan KY, Schwark M, Gyorgy A, Vogel T, Akopov S, Mitkovski M, Agoston D, Sestan N, Molnár Z, Tarabykin V (2008) Satb2 is a postmitotic determinant for upper-layer neuron specification in the neocortex. Neuron 57(3):378–392

    Article  CAS  PubMed  Google Scholar 

  • Burau K, Stenull I, Huber K, Misawa H, Berse B, Unsicker K, Ernsberger U (2004) c-ret regulates cholinergic properties in mouse sympathetic neurons: evidence from mutant mice. Eur J Neurosci 20(2):353–362

    Article  CAS  PubMed  Google Scholar 

  • Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Fariñas I, Karsenty G, Grosschedl R (2006) SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell 125(5):971–986

    Article  CAS  PubMed  Google Scholar 

  • Eiden LE (1998) The cholinergic gene locus. J Neurochem 70(6):2227–2240

    Article  CAS  PubMed  Google Scholar 

  • Ernsberger U (2001) The development of postganglionic sympathetic neurons: coordinating neuronal differentiation and diversification. Auton Neurosci 94(1–2):1–13

    Article  CAS  PubMed  Google Scholar 

  • Ernsberger U, Rohrer H (1999) Development of the cholinergic neurotransmitter phenotype in postganglionic sympathetic neurons. Cell Tissue Res 297(3):339–361

    Article  CAS  PubMed  Google Scholar 

  • Flett DL, Bell C (1991) Topography of functional subpopulations of neurons in the superior cervical ganglion of the rat. J Anat 177:55–66

    PubMed Central  CAS  PubMed  Google Scholar 

  • Francis NJ, Landis SC (1999) Cellular and molecular determinants of sympathetic neuron development. Annu Rev Neurosci 22:541–566

    Article  CAS  PubMed  Google Scholar 

  • Guidry G, Landis SC (1998) Target-dependent development of the vesicular acetylcholine transporter in rodent sweat gland innervation. Dev Biol 199(2):175–184

    Article  CAS  PubMed  Google Scholar 

  • Habecker BA, Landis SC (1994) Noradrenergic regulation of cholinergic differentiation. Science 264(5165):1602–1604

    Article  CAS  PubMed  Google Scholar 

  • Habecker BA, Sachs HH, Rohrer H, Zigmond RE (2009) The dependence on gp130 cytokines of axotomy induced neuropeptide expression in adult sympathetic neurons. Dev Neurobiol 69(6):392–400

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hendry IA (1977) Cell division in the developing sympathetic nervous system. J Neurocytol 6(3):299–309

    Article  CAS  PubMed  Google Scholar 

  • Howard MJ (2005) Mechanisms and perspectives on differentiation of autonomic neurons. Dev Biol 277(2):271–286

    Article  CAS  PubMed  Google Scholar 

  • Huber K, Ernsberger U (2006) Cholinergic differentiation occurs early in mouse sympathetic neurons and requires Phox2b. Gene Expr 13(2):133–139

    Article  CAS  PubMed  Google Scholar 

  • KamedaY Saitoh T, Nemoto N, Katoh T, Iseki S (2012) Hes1 is required for the development of the superior cervical ganglion of sympathetic trunk and the carotid body. Dev Dyn 241(8):1289–1300

    Article  Google Scholar 

  • Königsmark B (1970) Methods for the counting of neurons. In: Nauta WJ, Ebbesson S (eds) Contemporary research methods in neuroanatomy. Springer Verlag, Berlin

    Google Scholar 

  • Lo L, Morin X, Brunet JF, Anderson DJ (1999) Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells. Neuron 22(4):693–705

    Article  CAS  PubMed  Google Scholar 

  • Loy B, Apostolova G, Dorn R, McGuire VA, Arthur JS, Dechant G (2011) p38α and p38β mitogen-activated protein kinases determine cholinergic transdifferentiation of sympathetic neurons. J Neurosci 31(34):12059–12067

    Article  CAS  PubMed  Google Scholar 

  • Masliukov PM, Timmermans JP (2004) Immunocytochemical properties of stellate ganglion neurons during early postnatal development. Histochem Cell Biol 122(3):201–209

    Article  CAS  PubMed  Google Scholar 

  • Sarkar AA, Howard MJ (2006) Perspectives on integration of cell-extrinsic and cell-intrinsic pathways of signaling required for differentiation of noradrenergic sympathetic ganglion neurons. Auton Neurosci 126–127:225–231

    Article  PubMed  Google Scholar 

  • Schäfer MK, Schütz B, Weihe E, Eiden LE (1997) Target-independent cholinergic differentiation in the rat sympathetic nervous system. Proc Natl Acad Sci U S A 94(8):4149–4154

    Article  PubMed Central  PubMed  Google Scholar 

  • Schäfer MK, Eiden LE, Weihe E (1998) Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter II. The peripheral nervous system. Neuroscience 84(2):361–376

    Article  PubMed  Google Scholar 

  • Schmidt M, Lin S, Pape M, Ernsberger U, Stanke M, Kobayashi K, Howard MJ, Rohrer H (2009) The bHLH transcription factor Hand2 is essential for the maintenance of noradrenergic properties in differentiated sympathetic neurons. Dev Biol 329(2):191–200

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Schotzinger R, Yin X, Landis S (1994) Target determination of neurotransmitter phenotype in sympathetic neurons. J Neurobiol 25(6):620–639

    Article  CAS  PubMed  Google Scholar 

  • Schütz B, Schäfer MK, Eiden LE, Weihe E (1998) Vesicular amine transporter expression and isoform selection in developing brain, peripheral nervous system and gut. Brain Res Dev Brain Res 106(1–2):181–204

    Article  PubMed  Google Scholar 

  • Schütz B, Weihe E, Eiden LE (2001) Independent patterns of transcription for the products of the rat cholinergic gene locus. Neuroscience 104(3):633–642

    Article  PubMed  Google Scholar 

  • Schütz B, Mauer D, Salmon AM, Changeux JP, Zimmer A (2004) Analysis of the cellular expression pattern of beta-CGRP in alpha-CGRP-deficient mice. J Comp Neurol 476(1):32–43

    Article  PubMed  Google Scholar 

  • Schütz B, von Engelhardt J, Gördes M, Schäfer MK, Eiden LE, Monyer H, Weihe E (2008) Sweat gland innervation is pioneered by sympathetic neurons expressing a cholinergic/noradrenergic co-phenotype in the mouse. Neuroscience 156(2):310–318

    Article  PubMed Central  PubMed  Google Scholar 

  • Squire L, Berg D, Bloom FE, du Lac S, Ghosh A, Spitzer NC (2012) Fundamental Neuroscience, 4th edn. Elsevier B.V, Amsterdam

    Google Scholar 

  • Stanke M, Geissen M, Götz R, Ernsberger U, Rohrer H (2000) The early expression of VAChT and VIP in mouse sympathetic ganglia is not induced by cytokines acting through LIFRbeta or CNTFRalpha. Mech Dev 91(1–2):91–96

    Article  CAS  PubMed  Google Scholar 

  • Stanke M, Duong CV, Pape M, Geissen M, Burbach G, Deller T, Gascan H, Otto C, Parlato R, Schütz G, Rohrer H (2006) Target-dependent specification of the neurotransmitter phenotype: cholinergic differentiation of sympathetic neurons is mediated in vivo by gp 130 signaling. Development 133(1):141–150

    Article  CAS  PubMed  Google Scholar 

  • Szemes M, Gyorgy A, Paweletz C, Dobi A, Agoston DV (2006) Isolation and characterization of SATB2, a novel AT-rich DNA-binding protein expressed in development- and cell-specific manner in the rat brain. Neurochem Res 31(2):237–246

    Article  CAS  PubMed  Google Scholar 

  • Tafari AT, Thomas SA, Palmiter RD (1997) Norepinephrine facilitates the development of the murine sweat response but is not essential. J Neurosci 17(11):4275–4281

    CAS  PubMed  Google Scholar 

  • Weihe E, Schütz B, Hartschuh W, Anlauf M, Schäfer MK, Eiden LE (2005) Coexpression of cholinergic and noradrenergic phenotypes in human and nonhuman autonomic nervous system. J Comp Neurol 492(3):370–379

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Yang B, Slonimsky JD, Birren SJ (2002) A rapid switch in sympathetic neurotransmitter release properties mediated by the p75 receptor. Nat Neurosci 5(6):539–545

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Prof. Rudi Grosschedl (Max-Planck-Institute of Immunobiology and Epigenetics, Freiburg, Germany) for providing Satb2 mutant mice. We also thank Marion Zibuschka, Carola Gäckler, and Heidi Hlawaty for excellent technical assistance. Burkhard Schütz and Eberhard Weihe received financial support within the framework of LOEWE-Schwerpunkt ‘Non-Neuronal Cholinergic Systems’ of Justus Liebig University in Giessen, Germany.

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The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps-University, Robert-Koch-Straße 8, 35037, Marburg, Germany

    Burkhard Schütz, Martin K.-H. Schäfer, Markus Gördes & Eberhard Weihe

  2. Section on Molecular Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    Lee E. Eiden

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  1. Burkhard Schütz
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  2. Martin K.-H. Schäfer
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  3. Markus Gördes
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  4. Lee E. Eiden
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  5. Eberhard Weihe
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Correspondence to Burkhard Schütz or Eberhard Weihe.

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Schütz, B., Schäfer, M.KH., Gördes, M. et al. Satb2-Independent Acquisition of the Cholinergic Sudomotor Phenotype in Rodents. Cell Mol Neurobiol 35, 205–216 (2015). https://doi.org/10.1007/s10571-014-0113-2

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  • DOI: https://doi.org/10.1007/s10571-014-0113-2

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