The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Distinct Transcriptomes Define Rostral and Caudal Serotonin Neurons
Open accessAbstract
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(+) and Hmx(+)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.
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“Pioneering work has introduced the molecular diversity of serotonin neurons across the midbrain and hindbrain (Okaty et al., 2015; Spaethling et al., 2014; Wylie et al., 2010), yet systematic analysis and integration of multiple cellular characteristics at single-cell resolution within each raphe nucleus is still lacking.”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as Wylie et al., 2010
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Items 101–103 of 103
Human hindbrain organoids with segment-specific 5-HT neurons for motor modulationPreprint
Zhu, J., Pang, W., Liu, Y., Yin, Y., Lu, X., Wei, J., Jiang, L., Zhou, W., Cao, Y., Zhang, Q., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.27.726154
Pre-Existing Serotonergic Pathways Guide the Navigation of Developing Serotonergic AxonsPreprint
Picchi, M., Migliarini, S., Nazzi, S., Gianni, G., Janušonis, S., Barsotti, N., & Pasqualetti, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.09.04.749432
Chiu, I. M., Barrett, L. B., Williams, E., Strochlic, D. E., Lee, S., Weyer, A. D., Lou, S., Bryman, G., Roberson, D. P., Ghasemlou, N., et al. (2014) · Data Archiving and Networked Services (DANS) · doi:10.5061/dryad.dk68t.1
Metadata
- Authors
- Wylie, C. J., Hendricks, T. J., Zhang, B., Wang, L., Lu, P., Leahy, P., Fox, S., Maeno, H., & Deneris, E. S.
- Affiliations
- Case Western Reserve University (US)
- Salk Institute for Biological Studies (US)
- Vanderbilt University (US)
- Case Comprehensive Cancer Center (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-01-13
- Volume
- 30
- Issue
- 2
- Pages
- 670-684
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3403750
- OpenAlex
- W2041052894
- Cited by
- 104
- References
- 71
- Citations by year
- 2026: 4 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 11 · 2016: 7 · 2015: 8 · 2014: 13 · 2013: 9 · 2012: 10
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vanderbilt University
- Case Western Reserve University
- National Institute of Mental Health (P50MH078028, MH078028, R01MH062723)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Keywords
- serotonergic neurons, neuronal heterogeneity, Hox genes, engrailed, axon guidance, cell adhesion, neurodevelopmental disorders, transcriptome
- MeSH terms
- Age Factors, Analysis of Variance, Animals, Bacterial Proteins, Embryo, Mammalian, Flow Cytometry, Luminescent Proteins, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Rhombencephalon, Serotonin, Cluster Analysis, Homeodomain Proteins, Gene Expression Regulation, Developmental, Computational Biology, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice
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