HOXA5 localization in postnatal and adult mouse brain is suggestive of regulatory roles in postmitotic neurons

Abstract

Hoxa5 is a member of the Hox gene family, which plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. Hoxa5 expression in the adult mouse brain has been reported, suggesting that this gene may be functionally required in the brain after birth. To provide further insight into the Hoxa5 expression pattern and potential functions in the brain, we have characterized its neuroanatomical profile from embryonic stages to adulthood. While most Hox mapping studies have been based solely on transcript analysis, we extended our analysis to HOXA5 protein localization in adulthood using specific antibodies. Our results show that Hoxa5 expression appears in the most caudal part of the hindbrain at fetal stages, where it is maintained until adulthood. In the medulla oblongata and pons, we detected Hoxa5 expression in many precerebellar neurons and in several nuclei implicated in the control of autonomic functions. In these territories, the HOXA5 protein is present solely in neurons, specifically in γ-aminobutyric acid (GABA)ergic, glutamatergic, and catecholaminergic neurons. Finally, we also detected Hoxa5 transcripts, but not the HOXA5 protein, in the thalamus and the cortex, from postnatal stages to adult stages, and in the cerebellum at adulthood. We provide evidence that some larger variants of Hoxa5 transcripts are present in these territories. Our mapping analysis allowed us to build hypotheses regarding HOXA5 functions in the nervous system after birth, such as a potential role in the establishment and refinement/plasticity of precerebellar circuits during postnatal and adult life. J. Comp. Neurol. 525:1155-1175, 2017. © 2016 Wiley Periodicals, Inc.

Conditional Loss of Hoxa5 Function Early after Birth Impacts on Expression of Genes with Synaptic Function

“…Zic genes encoding transcription factors were also selected based on their known expression and critical function in mossy fibers precerebellar neurons ( Dipietrantonio and Dymecki, 2009 ). For quantitative analysis through RT-qPCR, we improved the resolution of the analysis by measuring RNA levels of the selected genes in dissected pons and caudal part of the medulla oblongata since HOXA5 expression was shown to be enriched in these restricted areas (Supplementary Figure S1 ) ( Lizen et al, 2017 ).…”

“…A key feature of Hoxa5 expression in the postnatal and adult hindbrain is its enrichment in precerebellar nuclei in the pons and medulla oblongata ( Lizen et al, 2017 ). Neurons of the precerebellar system, which relay both peripheral sensation and cortical input to the cerebellum, derive from the caudal part of the rhombic lip (r6–r8), using tangential migration to reach their final position.…”

“…Hoxa5 , a member of Hox PG5, is known for its numerous activities during development ( Jeannotte et al, 2016 ) and, together with its paralog genes, for its implication in different processes of fetal CNS development ( Philippidou et al, 2012 ; Di Meglio et al, 2013 ; Catela et al, 2016 ). In the hindbrain at fetal stages, Hoxa5 expression is detected in the caudal part of the medulla oblongata and in the posterior pontine region, where it participates in the tangential migration of precerebellar neurons from the rhombic lip toward the pontine gray (PG) nucleus ( Di Meglio et al, 2013 ; Tomas-Roca et al, 2016 ; Lizen et al, 2017 ). Indeed, PG5 HOX proteins are shown to be functionally implicated in the topographic organization of migrating precerebellar pontine neurons, through the negative regulation of Unc5b expression, a netrin repulsive receptor ( Di Meglio et al, 2013 ).…”

“…A key feature of this analysis was the enrichment of Hoxa5 transcripts in pontine and medullary precerebellar neurons. They are also detected in different nuclei implicated in the control of autonomic functions ( Lizen et al, 2017 ). In these territories, the HOXA5 protein is specifically present in neurons, and principally in glutamatergic and GABAergic neurons.…”

Down-regulation of HOXB5 inhibits TGF-β-induced migration and invasion in hepatocellular carcinoma cellsviainactivation of the PI3K/Akt pathway

“…HOXB5, a member of the HOX gene family, is known as a crucial player in development of the enteric nervous system. 27,28 In addition, abnormalities in HOXB5 functions may cause Hirschsprung's disease. 29,30 Recently, HOXB5 was reported to be associated with cancer progression.…”