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

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 +1 more·2013·Brain Structure and Function

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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Research works printed but not linked: 6

  1. Azmitia EC Gannon PJ Anatomy of the serotonergic system in the primate and sub-primate brain Adv Neurol 1986 43 407 468 2418648
  2. Cambronero F Aportaciones a la organización estructural del rombencéfalo de pollo. Dissertation 1999 Spain University of Murcia
  3. Puelles E Martínez-de-la-Torre M Watson C Puelles L Watson C Paxinos G Puelles L Midbrain The mouse nervous system 2012 San Diego Academic Press-Elsevier 338 359
  4. Swanson LW (1998) Brain maps: structure of the rat brain. 2nd rev edn., Elsevier, Amsterdam
  5. Swanson LW Brain architecture 2003 Oxford/New York Oxford Univ Press
  6. Watson C Watson C Paxinos G Puelles L Hindbrain The mouse nervous system 2012 San Diego Elsevier Academic Press 398 423

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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
Venue
Brain Structure and Function
Published
2012-09-30
Volume
218
Issue
5
Pages
1229-1277
ISSN
  • 1863-2653 (ISSN-L)
  • 1863-2661
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
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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