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Download Ciliated dendrite mRNA may control olfactory sensory neuron
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Ciliated dendrite mRNA may control olfactory sensory neuron survival and death Marie-Annick Persuy (INRA NOPA), Monique Caillol (INRA NOPA), P Benesh (Genenoscience), Christine Formisano-Tréziny (UII. ERT MEIDIA), Jean Gabert (UMAGT), Jean-Jacques Remy (USC INRA-Phase NICN CNRS UMR 6184) Important to both developmental and neurobiological function, localized translation of specific sets of mRNA allows for asymetric distribution of gene products. Local translation in neuron dendritic or axonal endings, is though to control neurite growth, formation of synapses and rapid responses to external stimuli. Olfactory sensory neurons (OSN) are the only neurons exposed to the external environment via their ciliated dendrites that express the odor receptors. Since there is no blood-brain barrier in the olfactory region, OSN participate to the brain protection against airborne toxic chemicals, infectious agents and parasitic genetic elements. OSN are short living cells constantly renewed from progenitors. The life-long regeneration of OSN represents one of the only few instances of adult neurogenesis in the central nervous system. It has raised high interest in dissecting the pathways for neural development, differentiation and survival. Odorant stimulation protects OSN from dying. OSN survival thus depends on an efficient defense against external aggressions but also on odor-induced activation of “survival” genes. A cDNA library, named ONCL for Olfactory Neuron Ciliae Library, was generated from purified rat OSN ciliated dendrites. Sequencing of the library led to the identification of more than 300 genes that might be locally translated within OSN ciliae. We then purified OSN ciliae RNA from seven different animals and analysed expression levels of several ONCL genes in each individual. Using quantitative PCR, we evaluated OSN cilia expression of the five following ONCL genes : PP1 (Phosphatase 1), CIRBP (Cold-Inducible RNA Binding Protein), APP (Amyloid Precursor Protein), Tsn (Translin) and Ssr3 (member of the translocon complex). We found that the five genes expressed at the same levels in OSN cilia from seven different animals. Consistent with the unique features of OSN, i.e. brain-environment interface and activity-dependent survival, functional analysis of all ONCL genes revealed that more than half of them encode “survival” proteins. Interestingly, a large set of ONCL genes belong to the odor-evoked p38/MAPK pathway, which is also a conserved innate immunity pathway. Besides a number of expected immune and defense genes, we identified a number of tumor promoter and cell cycle control genes, suggesting the existence of new links between activity and survival via oncogenic and antiapoptotic mechanisms.