Cited by 113Developmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanismsNeurotransmitter Receptor Influence on Behavior

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Development of the serotonergic cells in murine raphe nuclei and their relations with rhombomeric domains

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Alonso, Antonia, Merchán, Paloma, Sandoval, Juan E., Sánchez-Arrones, Luisa, Garcia-Cazorla, Angels, Artuch, Rafael, Ferrán, José L., Martínez-de-la-Torre, Margaret, Puelles, Luis·2013·Brain Structure and Function

DOI 10.1007/s00429-012-0456-8PMC PMC3748323

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Abstract

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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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
ORCID: Alonso, Antonia
Merchán, Paloma
Artuch, Rafael
Ferrán, José L.
Puelles, Luis
Venue: Brain Structure and Function
Publisher: Springer Science and Business Media LLC
Published: 2012-09-30
Volume: 218
Issue: 5
Pages: 1229-1277
ISSN: 1863-2653 (ISSN-L)
1863-2661
DOI: 10.1007/s00429-012-0456-8
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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Development of the serotonergic cells in murine raphe nuclei and their relations with rhombomeric domains

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