Systematic expression analysis of Hox genes at adulthood reveals novel patterns in the central nervous system

• DOI: 10.1007/s00429-014-0965-8
• Publication Date: 2014-12-19T11:42:11Z
• Authors: Bertrand Hutlet; Nicolas Theys; Cécile Coste; Marie-Thérèse Ahn; Konstantin Doshis...; Benoît Lizen; Françoise Gofflot
• Keywords: Male; Neurons; 0301 basic medicine; precerebellar nuclei; Reverse Transcriptase Polymerase Chain Reaction; forebrain; RT-qPCR; Genes, Homeobox; Brain; Gene Expression Regulation, Developmental; 3. Good health; Mice, Inbred C57BL; Hox genes; Mice; 03 medical and health sciences; Animals; sensory circuits; in situ hybridization; Transcriptome; hindbrain; In Situ Hybridization

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.