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

is a member of the gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, transcripts are enriched in many precerebellar neurons and several nuclei involved in autonomic functions, while the HOXA5 protein is detected mainly in glutamatergic and GABAergic neurons. However, whether HOXA5 is functionally required in these neurons after birth remains unknown. As a first approach to tackle this question, we aimed at determining the molecular programs downstream of the HOXA5 transcription factor in the context of the postnatal brainstem. A comparative transcriptomic analysis was performed in combination with gene expression localization, using a conditional postnatal loss-of-function mouse model. After inactivation of at postnatal days (P)1-P4, we established the transcriptome of the brainstem from P21 conditional mutants using RNA-Seq analysis. One major finding was the downregulation of several genes associated with synaptic function in mutant specimens including different actors involved in glutamatergic synapse, calcium signaling pathway, and GABAergic synapse. Data were confirmed and extended by reverse transcription quantitative polymerase chain reaction analysis, and the expression of several HOXA5 candidate targets was shown to co-localize with transcripts in precerebellar nuclei. Together, these new results revealed that HOXA5, through the regulation of key actors of the glutamatergic/GABAergic synapses and calcium signaling, might be involved in synaptogenesis, synaptic transmission, and synaptic plasticity of the cortico-ponto-cerebellar circuitry in the postnatal brainstem.