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Redefining the serotonergic system by genetic lineage

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Abstract

Central serotonin-producing neurons are heterogeneous—differing in location, morphology, neurotoxin sensitivity and associated clinical disorders—but the underpinnings of this heterogeneity are largely unknown, as are the markers that distinguish physiological subtypes of serotonergic neurons. Here we redefined serotonergic subtypes on the basis of genetic programs that are differentially enacted in progenitor cells. We uncovered a molecular framework for the serotonergic system that, having genetic lineages as its basis, is likely to have physiological relevance and will permit access to genetically defined subtypes for manipulation.

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Figure 1: Intersectional and subtractive cell marking distinguishes r1 (En1-cre)- from non–r1-derived 5-HT neurons.
Figure 2: 5-HT neuron organization, as defined by embryonic origin and developmental gene expression profile, differs from that determined by anatomical architecture.
Figure 3: r1 (En1-cre)- and non–r1-derived 5-HT neurons populate the postnatal Nkx2.2−/− mutant brainstem.

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References

  1. Paterson, D.S. et al. J. Am. Med. Assoc. 296, 2124–2132 (2006).

    Article  CAS  Google Scholar 

  2. Riikonen, R.S. et al. Biol. Psychiatry 57, 1565–1572 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Pardo, C.A. & Eberhart, C.G. Brain Pathol. 17, 434–447 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Lidov, H.G. & Molliver, M.E. Brain Res. Bull. 8, 389–430 (1982).

    Article  CAS  PubMed  Google Scholar 

  5. Cordes, S.P. Clin. Genet. 68, 487–494 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Lumsden, A. & Krumlauf, R. Science 274, 1109–1115 (1996).

    Article  CAS  PubMed  Google Scholar 

  7. Farago, A.F. et al. Neuron 50, 205–218 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Awatramani, R. et al. Nat. Genet. 35, 70–75 (2003).

    Article  CAS  PubMed  Google Scholar 

  9. Dymecki, S.M. & Kim, J.C. Neuron 54, 17–34 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kimmel, R.A. et al. Genes Dev. 14, 1377–1389 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Zervas, M. et al. Neuron 43, 345–357 (2004).

    Article  CAS  PubMed  Google Scholar 

  12. Simon, H.H. et al. Mol. Cell. Neurosci. 28, 96–105 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Voiculescu, O. et al. Genesis 26, 123–126 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Wallace, J.A. et al. Brain Res. Bull. 9, 117–129 (1982).

    Article  CAS  PubMed  Google Scholar 

  15. Scott, M.M. et al. J. Neurosci. 25, 2628–2636 (2005).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank A. Joyner, S. Schneider-Maunoury, and L. Sussel for mice (En1-cre, Egr2-cre and Nkx2.2+/−, respectively), and C. Cepko and L. Murtaugh for plasmids. We also thank members of the Dymecki lab and SIDS PPG (P01 HD036379) for input. This work was supported by grants from the US National Institutes of Health (P01 HD036379, R01 DK 067826 and R21 DA023643 to S.M.D., and R01 MH62723 to E.S.D.), the Charles H. Hood Foundation (P.J.) and the Charles King Trust Foundation (R.B.A.).

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Author notes

  1. Patricia Jensen, Anna F Farago and Rajeshwar B Awatramani: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, 02115, Massachusetts, USA

    Patricia Jensen, Anna F Farago & Susan M Dymecki

  2. Department of Neurology and Center for Genetic Medicine, Northwestern University Feinberg Medical School, 7-113 Lurie, 303 E. Superior St., Chicago, 60611, Illinois, USA

    Rajeshwar B Awatramani

  3. Department of Neurosciences, Case Western Reserve University, School of Medicine, Room E653, 10900 Euclid Avenue, Cleveland, 44106-4975, Ohio, USA

    Michael M Scott & Evan S Deneris

Authors
  1. Patricia Jensen
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  2. Anna F Farago
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  3. Rajeshwar B Awatramani
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  4. Michael M Scott
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  5. Evan S Deneris
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  6. Susan M Dymecki
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Corresponding author

Correspondence to Susan M Dymecki.

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Jensen, P., Farago, A., Awatramani, R. et al. Redefining the serotonergic system by genetic lineage. Nat Neurosci 11, 417–419 (2008). https://doi.org/10.1038/nn2050

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  • DOI: https://doi.org/10.1038/nn2050

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