Distinct transcriptomes define rostral and caudal serotonin neurons

Christi J. Wylie, Timothy J. Hendricks, Bing Zhang, Lily Wang, Pengcheng Lu, Patrick Leahy, Stephanie Fox, Hiroshi Maeno, Evan S. Deneris

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84 Scopus citations

Abstract

The molecular architecture of developing serotonin (5HT) neurons is poorly understood, yet its determination is likely to be essential for elucidating functional heterogeneity of these cells and the contribution of serotonergic dysfunction to disease pathogenesis. Here, we describe the purification of postmitotic embryonic 5HT neurons by flow cytometry for whole-genome microarray expression profiling of this unitary monoaminergic neuron type. Our studies identified significantly enriched expression of hundreds of unique genes in 5HT neurons, thus providing an abundance of new serotonergic markers. Furthermore, we identified several hundred transcripts encoding homeodomain, axon guidance, cell adhesion, intracellular signaling, ion transport, and imprinted genes associated with various neurodevelopmental disorders that were differentially enriched in developing rostral and caudal 5HT neurons. These findings suggested a homeodomain code that distinguishes rostral and caudal 5HT neurons. Indeed, verification studies demonstrated that Hmx homeodomain and Hox gene expression defined an Hmx+ rostral subtype and Hox+ caudal subtype. Expression of engrailed genes in a subset of 5HT neurons in the rostral domain further distinguished two subtypes defined as Hmx+En +andHmx+En-. The differential enrichment of gene sets for different canonical pathways and gene ontology categories provided additional evidence for heterogeneity between rostral and caudal 5HT neurons. These findings demonstrate a deep transcriptome and biological pathway duality for neurons that give rise to the ascending and descending serotonergic subsystems. Our databases provide a rich, clinically relevant resource for definition of 5HT neuron subtypes and elucidation of the genetic networks required for serotonergic function.

Original languageEnglish (US)
Pages (from-to)670-684
Number of pages15
JournalJournal of Neuroscience
Volume30
Issue number2
DOIs
StatePublished - Jan 13 2010
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Wylie, C. J., Hendricks, T. J., Zhang, B., Wang, L., Lu, P., Leahy, P., Fox, S., Maeno, H., & Deneris, E. S. (2010). Distinct transcriptomes define rostral and caudal serotonin neurons. Journal of Neuroscience, 30(2), 670-684. https://doi.org/10.1523/JNEUROSCI.4656-09.2010