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Redefining the serotonergic system by genetic lineage

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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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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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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