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Visceral motor neuron diversity delineates a cellular basis for nipple- and pilo-erection muscle control

Nature Neuroscience volume 19, pages 13311340 (2016) | Download Citation

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Despite the variety of physiological and target-related functions, little is known regarding the cellular complexity in the sympathetic ganglion. We explored the heterogeneity of mouse stellate and thoracic ganglia and found an unexpected variety of cell types. We identified specialized populations of nipple- and pilo-erector muscle neurons. These neurons extended axonal projections and were born among other neurons during embryogenesis, but remained unspecialized until target organogenesis occurred postnatally. Target innervation and cell-type specification was coordinated by an intricate acquisition of unique combinations of growth factor receptors and the initiation of expression of concomitant ligands by the nascent erector muscles. Overall, our results provide compelling evidence for a highly sophisticated organization of the sympathetic nervous system into discrete outflow channels that project to well-defined target tissues and offer mechanistic insight into how diversity and connectivity are established during development.

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  • 05 September 2016

    In the version of this article initially published online, the symbols were reversed in the key for Figure 2l. The error has been corrected for the print, PDF and HTML versions of this article.


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We thank S. Arber (Friedrich Miescher Institute for Biomedical Research) for kindly providing the TaumGFP mouse line, and J.-F. Brunet (Institut de Biologie de l'École Normale Supérieure), T. Müller (The Max Delbrück Center for Molecular Medicine) and T. Taija Mäkinen (Uppsala University) for generously providing PHOX2B, TLX3 and PROX1 antibodies, respectively. We also thank S. Lücke and J. Sontheimer for technical support, and J. Hjerling-Leffler (Karolinska Institutet) for reagents. This work was supported by the Swedish Medical Research Council, Knut and Alice Wallenbergs Foundation (Wallenberg Scholar and for CLICK imaging facility), SFO grant (DBRM), Swedish Cancer Foundation, Söderbergs Foundation and Karolinska Institutet (P.E.), Knut and Alice Wallenberg's Foundation (2015.0041), Swedish Research Council (STARGET), Swedish foundation for strategic research (RIF14-0057) (to S.L.).

Author information


  1. Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

    • Alessandro Furlan
    • , Gioele La Manno
    • , Moritz Lübke
    • , Martin Häring
    • , Hind Abdo
    • , Hannah Hochgerner
    • , Dmitry Usoskin
    • , Sten Linnarsson
    •  & Patrik Ernfors
  2. Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

    • Jussi Kupari
    •  & Matti S Airaksinen
  3. Center for Vascular and Developmental Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

    • Guillermo Oliver


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A.F. and P.E. designed the study. P.E. supervised the study and S.L. supervised the single-cell RNA-seq experiments. A.F. performed most of the experiments, analyzed the data and prepared the figures. A.F., M.H., G.L.M., H.H. and D.U. dissected, dissociated captured SG single cells and prepared cDNA libraries. G.L.M. performed single-cell analysis and prepared these figures. M.L. bred TrkACre, RetCFP and Retfl mouse lines and processed the tissues. M.L. and H.A. performed fate-tracing experiments. J.K. and M.S.A. provided Gfra2KO tissue. G.O. provided Prox1floxed mice. A.F. and P.E. wrote the paper, with input from all of the other authors.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Sten Linnarsson or Patrik Ernfors.

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    Supplementary Text and Figures

    Supplementary Figures 1–13

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    Supplementary Methods Checklist

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  1. 1.

    Supplementary Table 1: Single cell mRNA expression.

    The complete transcriptome is reported for each single cell. Values are transcript molecules counts estimated by using UMI. The assigned cluster (i.e. NA1, NA2, etc) and cell areas of single cells are also indicated.

  2. 2.

    Supplementary Table 2: Complete expression patterns.

    For each detected gene the average number of detected mRNA molecules expressed by each of the neuronal types is indicated.

  3. 3.

    Supplementary Table 3: Markers for sympathetic neurons.

    List of genes over-expressed in each population. Maximum a posteriori probability (MAP) estimates of the average number of molecules per cell are indicated for each population and baseline.

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