Abstract
The protein doublecortin is mainly expressed in migrating neuroblasts and immature neurons. The X-linked gene MECP2, associated to several neurodevelopmental disorders such as Rett syndrome, encodes the protein methyl-CpG-binding protein 2 (MeCP2), a regulatory protein that has been implicated in neuronal maturation and refinement of olfactory circuits. Here, we explored doublecortin immunoreactivity in the brain of young adult female Mecp2-heterozygous and male Mecp2-null mice and their wild-type littermates. The distribution of doublecortin-immunoreactive somata in neurogenic brain regions was consistent with previous reports in rodents, and no qualitative differences were found between genotypes or sexes. Quantitatively, we found a significant increase in doublecortin cell density in the piriform cortex of Mecp2-null males as compared to WT littermates. A similar increase was seen in a newly identified population of doublecortin cells in the olfactory tubercle. In these olfactory structures, however, the percentage of doublecortin immature neurons that also expressed NeuN was not different between genotypes. By contrast, we found no significant differences between genotypes in doublecortin immunoreactivity in the olfactory bulbs. Nonetheless, in the periglomerular layer of Mecp2-null males, we observed a specific decrease of immature neurons co-expressing doublecortin and NeuN. Overall, no differences were evident between Mecp2-heterozygous and WT females. In addition, no differences could be detected between genotypes in the density of doublecortin-immunoreactive cells in the hippocampus or striatum of either males or females. Our results suggest that MeCP2 is involved in neuronal maturation in a region-dependent manner.
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Abbreviations
- Aca:
-
Anterior commissure
- AcbC:
-
Nucleus accumbens core
- AOB:
-
Accessory olfactory bulb
- AOL:
-
Anterior olfactory nucleus, lateral
- AOM:
-
Anterior olfactory nucleus, medial
- AOV:
-
Anterior olfactory nucleus, ventral
- CC:
-
Corpus callosum
- CPu:
-
Caudatus putamen
- DG:
-
Dentate gyrus
- dSt:
-
Dorsal striatum
- Gl:
-
Glomerular cell layer of the olfactory bulb
- Gr:
-
Granular cell layer of the olfactory bulb
- GrDG:
-
Granular layer of the dentate gyrus
- LV:
-
Lateral ventricle
- Mi:
-
Mitral cell layer of the olfactory bulb
- Mol:
-
Molecular layer of the dentate gyrus
- OB:
-
Olfactory bulbs
- Pir:
-
Piriform cortex
- PGl:
-
Periglomerular layer of the olfactory bulb
- PoDG:
-
Polymorphic-oriens layer of the dentate gyrus
- RMS:
-
Rostral migratory stream
- SVZ:
-
Subventricular zone
- Tu:
-
Olfactory tubercle
- vSt:
-
Ventral striatum
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Acknowledgements
The authors are indebted to Marta Igual, Adriana Gregory-Flores and Rylie Frese for their help in cell counting, and to Dr Guillermo Ayala for statistical advice.
Funding
Funded by the Spanish Ministry of Education (BFU2016-77691-C2-1-P) to FMG and EL, Conselleria d’Educació, Investigació, Cultura i Esport (PROMETEO/2016/076) and Universitat Jaume I (UJI-B2016-45) to FMG, Spanish Ministry of Science, Competitiveness and Universities (SAF2015-68436-R) to JN, E-Rare-2 JTC 2012 and E-Rare-2 JTC 2014 by the German Federal Ministry of Education and Research (BMBF) [01GM1302 to M.S., 01GM1505 to O.S.]. Animals were treated throughout according to the protocols that were approved by the local veterinary office and carried out in strict accordance with the EU directive 2010/63/EU and the German law.
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Martínez-Rodríguez, E., Martín-Sánchez, A., Coviello, S. et al. Lack of MeCP2 leads to region-specific increase of doublecortin in the olfactory system. Brain Struct Funct 224, 1647–1658 (2019). https://doi.org/10.1007/s00429-019-01860-6
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DOI: https://doi.org/10.1007/s00429-019-01860-6