Dataset Information

Retinoic acid receptor-dependent survival of olfactory sensory neurons in postnatal and adult mice.

ABSTRACT: To address the hypothesis that retinoids produced by synthesizing enzymes present in the primary olfactory system influence the mouse olfactory sensory map, we expressed a dominant-negative retinoic acid receptor selectively in olfactory sensory neurons. We show that neurons deficient in nuclear retinoid signaling are responsive to odors and form correct odorant receptor-specific axonal projections to target neurons in the olfactory bulb of the brain. Subsequent to the formation of the map, the neurons die prematurely by retrograde-driven caspase-3 activation, which resembles the previously described mechanism of neural death after olfactory bulb ablation. This neurodegenerative event is initiated the second postnatal week and occurs in the adult animal without a compensatory increase of progenitor cell proliferation. In addition, we find that nuclear retinoid signaling is required for the expression of a retinoic acid-degrading enzyme, Cyp26B1, in a small fraction of mature neurons. Collectively, the results provide evidence for a role of locally regulated retinoid metabolism in neuroprotection and in determining population size of neurons at a late stage of neural circuit formation.

SUBMITTER: Hagglund M

PROVIDER: S-EPMC6674105 | biostudies-literature | 2006 Mar

REPOSITORIES: biostudies-literature

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Retinoic acid receptor-dependent survival of olfactory sensory neurons in postnatal and adult mice.

Hägglund Maria M Berghard Anna A Strotmann Jörg J Bohm Staffan S

The Journal of neuroscience : the official journal of the Society for Neuroscience 20060301 12

To address the hypothesis that retinoids produced by synthesizing enzymes present in the primary olfactory system influence the mouse olfactory sensory map, we expressed a dominant-negative retinoic acid receptor selectively in olfactory sensory neurons. We show that neurons deficient in nuclear retinoid signaling are responsive to odors and form correct odorant receptor-specific axonal projections to target neurons in the olfactory bulb of the brain. Subsequent to the formation of the map, the ...[more]

PMID: 16554478

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Project description:Stimulus-dependent expression of the retinoic acid-inactivating enzyme Cyp26B1 in olfactory sensory neurons (OSNs) forms a dorsomedial (DM)-ventrolateral (VL) gradient in the mouse olfactory epithelium. The gradient correlates spatially with different rates of OSN turnover, as well as the functional organization of the olfactory sensory map, into overlapping zones of OSNs that express different odorant receptors (ORs). Here, we analyze transgenic mice that, instead of a stimulus-dependent Cyp26B1 gradient, have constitutive Cyp26B1 levels in all OSNs. Starting postnatally, OSN differentiation is decreased and progenitor proliferation is increased. Initially, these effects are selective to the VL-most zone and correlate with reduced ATF5 expression and accumulation of OSNs that do not express ORs. Transcription factor ATF5 is known to stabilize OR gene choice via onset of the stimulus-transducing enzyme adenylyl cyclase type 3. During further postnatal development of Cyp26B1 mice, an anomalous DM(high)-VL(low) expression gradient of adenylyl cyclase type 3 appears, which coincides with altered OR frequencies and OR zones. All OR zones expand ventrolaterally except for the VL-most zone, which contracts. The expansion results in an increased zonal overlap that is also evident in the innervation pattern of OSN axon terminals in olfactory bulbs. These findings together identify a mechanism by which postnatal sensory-stimulated vitamin A metabolism modifies the generation of spatially specified neurons and their precise topographic connectivity. The distributed patterns of vitamin A-metabolizing enzymes in the nervous system suggest the possibility that the mechanism may also regulate neuroplasticity in circuits other than the olfactory sensory map.Significance statementThe mouse olfactory sensory map is functionally wired according to precise axonal projections of spatially organized classes of olfactory sensory neurons in the nose. The genetically controlled mechanisms that regulate the development of the olfactory sensory map are beginning to be elucidated. Little is known about mechanisms by which sensory stimuli shape the organization of the map after birth. We show that a stimulus-dependent gradient of a retinoic acid-inactivating enzyme Cyp26B1 modifies the composition, localization, and axonal projections of olfactory sensory neuron classes. The mechanism is novel and suggests the interesting possibility that local vitamin A metabolism could also be a mediator of stimulus-dependent modifications of precise spatial connectivity in other parts of the nervous system.

Dataset Information

Retinoic acid receptor-dependent survival of olfactory sensory neurons in postnatal and adult mice.

Publications

Retinoic acid receptor-dependent survival of olfactory sensory neurons in postnatal and adult mice.

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