The Journal of Neuroscience, March 22, 2006, 26(12):3281-3291; doi:10.1523/JNEUROSCI.4955-05.2006
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Cellular/Molecular
Retinoic Acid Receptor-Dependent Survival of Olfactory Sensory Neurons in Postnatal and Adult Mice
Maria Hägglund,1
Anna Berghard,1
Jörg Strotmann,2 and
Staffan Bohm1
1Department of Molecular Biology, Umeå University, SE901 87 Umeå, Sweden, and 2Institute of Physiology, University of Hohenheim, D-70593 Stuttgart, Germany
Correspondence should be addressed to Staffan Bohm, Department of Molecular Biology, Umeå University, Umeå, SE901 87 Sweden. Email: staffan.bohm{at}molbiol.umu.se
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.
Key words: apoptosis; neuron; olfactory; RAR; postnatal; retinoic acid
Received Nov. 21, 2005;
revised Feb. 7, 2006;
accepted Feb. 7, 2006.
Correspondence should be addressed to Staffan Bohm, Department of Molecular Biology, Umeå University, Umeå, SE901 87 Sweden. Email: staffan.bohm{at}molbiol.umu.se
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