Abstract
Hox proteins are key regulators of animal development, providing positional identity and patterning information to cells along the rostrocaudal axis of the embryo. Although their embryonic expression and function are well characterized, their presence and biological importance in adulthood remains poorly investigated. We provide here the first detailed quantitative and neuroanatomical characterization of the expression of the 39 Hox genes in the adult mouse brain. Using RT-qPCR we determined the expression of 24 Hox genes mainly in the brainstem of the adult brain, with low expression of a few genes in the cerebellum and the forebrain. Using in situ hybridization (ISH) we have demonstrated that expression of Hox genes is maintained in territories derived from the early segmental Hox expression domains in the hindbrain. Indeed, we show that expression of genes belonging to paralogy groups PG2-8 is maintained in the hindbrain derivatives at adulthood. The spatial colinearity, which characterizes the early embryonic expression of Hox genes, is still observed in sequential antero-posterior boundaries of expression. Moreover, the main mossy and climbing fibres precerebellar nuclei express PG2-8 Hox genes according to their migration origins. Second, ISH confirms the presence of Hox gene transcripts in territories where they are not detected during development, suggesting neo-expression in these territories in adulthood. Within the forebrain, we have mapped Hoxb1, Hoxb3, Hoxb4, Hoxd3 and Hoxa5 expression in restricted areas of the sensory cerebral cortices as well as in specific thalamic relay nuclei. Our data thus suggest a requirement of Hox genes beyond their role of patterning genes, providing a new dimension to their functional relevance in the central nervous system.
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19 January 2021
Editor’s Note: Readers are alerted that concerns have been raised regarding Figures 2C and 2D. We will update readers once we have further information and all parties have been given an opportunity to respond in full.
18 March 2021
A Correction to this paper has been published: https://doi.org/10.1007/s00429-021-02252-5
Abbreviations
- AMS:
-
Anterior extramural migrating stream
- AP:
-
Area postrema
- A/P:
-
Antero-posterior
- BS:
-
Brainstem
- Cb:
-
Cerebellum
- CNS:
-
Central nervous system
- Cx:
-
Cerebral cortex
- dmX:
-
Dorsal nucleus of the vagus nerve
- ECU:
-
External cuneate
- Hi:
-
Hippocampus
- Hy:
-
Hypothalamus
- IF5:
-
Interfascicular trigeminal nucleus
- IHC:
-
Immunohistochemistry
- IO:
-
Inferior olive
- ISH:
-
In situ hybridization
- PBS:
-
Phosphate-buffered saline
- IMS:
-
Intramural migrating stream
- LGd:
-
Dorsal lateral geniculate nucleus
- LRN:
-
Lateral reticular nucleus
- MG:
-
Medial geniculate nucleus
- MNs:
-
Motoneurons
- MO:
-
Medulla oblongata
- NTS:
-
Nucleus of the solitary tract
- OA:
-
Olfactory areas
- PCs:
-
Purkinje cells
- PMS:
-
Posterior extramural migrating stream
- PG:
-
Paralogy groups
- PN:
-
Pontine nucleus
- Po:
-
Pons
- PrV:
-
Principal sensory trigeminal nucleus
- r:
-
Rhombomere
- RO:
-
Raphe obscurus
- RPA:
-
Raphe pallidus
- SC:
-
Spinal cord
- SpV:
-
Spinal trigeminal nucleus
- Th:
-
Thalamus
- TRN:
-
Tegmental reticular nucleus
- VPL:
-
Ventral posterolateral nucleus of the thalamus
- VPM:
-
Ventral posteromedial nucleus of the thalamus
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Acknowledgments
The authors want to thank Coralie Piget for animal husbandry, and Arnaud Van Hecke and Jean-François de Backer for their contribution in setting up the procedures. We are grateful to René Rezsohazy and Bernard Knoops for helpful discussions and comments on the manuscript and Helen Christian for critical reading. This work was supported by the Fonds de la Recherche Scientifique-FNRS under Grant MIS-Ulysse n °F.6003.09, by the Fonds Spéciaux de Recherche of the Université catholique de Louvain, and by the «Communauté française de Belgique-Actions de Recherche Concertées» (12/17-041). B.L. is a FRIA fellow of the Fonds de la Recherche Scientifique-FNRS.
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Hutlet, B., Theys, N., Coste, C. et al. Systematic expression analysis of Hox genes at adulthood reveals novel patterns in the central nervous system. Brain Struct Funct 221, 1223–1243 (2016). https://doi.org/10.1007/s00429-014-0965-8
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DOI: https://doi.org/10.1007/s00429-014-0965-8