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Development of the serotonergic cells in murine raphe nuclei and their relations with rhombomeric domains
Open accessAbstract
The raphe nuclei represent the origin of central serotonergic projections. The literature distinguishes seven nuclei grouped into rostral and caudal clusters relative to the pons. The boundaries of these nuclei have not been defined precisely enough, particularly with regard to developmental units, notably hindbrain rhombomeres. We hold that a developmental point of view considering rhombomeres may explain observed differences in connectivity and function. There are twelve rhombomeres characterized by particular genetic profiles, and each develops between one and four distinct serotonergic populations. We have studied the distribution of the conventional seven raphe nuclei among these twelve units. To this aim, we correlated 5-HT-immunoreacted neurons with rhombomeric boundary landmarks in sagittal mouse brain sections at different developmental stages. Furthermore, we performed a partial genoarchitectonic analysis of the developing raphe nuclei, mapping all known serotonergic differentiation markers, and compared these results, jointly with others found in the literature, with our map of serotonin-containing populations, in order to examine regional variations in correspondence. Examples of regionally selective gene patterns were identified. As a result, we produced a rhombomeric classification of some 45 serotonergic populations, and suggested a corresponding modified terminology. Only a minor rostral part of the dorsal raphe nucleus lies in the midbrain. Some serotonergic neurons were found in rhombomere 4, contrary to the conventional assumption that it lacks such neurons. We expect that our reclassification of raphe nuclei may be useful for causal analysis of their differential molecular specification, as well as for studies of differential connectivity and function.
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“DR serotonin neurons derive entirely from rhombomere 1 of the developing mouse brain, whereas MR serotonin neurons derive predominantly from rhombomeres 1, 2, and 3 (Alonso et al., 2013; Bang et al., 2012; Jensen et al., 2008).”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as Alonso et al., 2013
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“Evidence has suggested that the DR and MR serotonin systems differ in developmental origin, connectivity, physiology, and behavioral function (Alonso et al., 2013; Calizo et al., 2011; Okaty et al., 2019).”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as Alonso et al., 2013
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The mood stabilizer lithium alters behaviour and physiology via the gut brain axisPreprint
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Metadata
- Authors
- Alonso, A., Merchán, P., Sandoval, J. E., Sánchez-Arrones, L., Garcia-Cazorla, A., Artuch, R., Ferrán, J. L., Martínez-de-la-Torre, M., & Puelles, L.
- Affiliations
- Universidad de Murcia (ES)
- Cincinnati Children's Hospital Medical Center (US)
- Institut du Thorax (FR)
- Hospital Sant Joan de Déu Barcelona (ES)
- Corresponding author
- Puelles, Luis
- Venue
- Brain Structure and Function
- Published
- 2012-09-30
- Volume
- 218
- Issue
- 5
- Pages
- 1229-1277
- ISSN
- 1863-2653 (ISSN-L)
- 1863-2661
- PMC
- PMC3748323
- OpenAlex
- W2086520973
- Cited by
- 113
- References
- 208
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 10 · 2019: 9 · 2018: 9 · 2017: 11 · 2016: 12 · 2015: 10 · 2014: 10 · 2013: 6 · 2012: 1
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Brain Structure and Function (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- National Institutes of Health (5r01mh070370-04)
- National Institute of Mental Health (R01 MH070370, 1R01 MH 070370-01A2)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- serotonergic neurons, raphe nuclei, rhombomeres, dorsal raphe nucleus, serotonin immunoreactivity, hindbrain development, rhombomere 4, mouse brain development
- MeSH terms
- Animals, Image Processing, Computer-Assisted, Immunohistochemistry, Terminology as Topic, Raphe Nuclei, Rhombencephalon, Serotonin, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Mice, Serotonergic Neurons
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