The Journal of Neuroscience, April 9, 2008, 28(15):3966-3975; doi:10.1523/JNEUROSCI.5625-07.2008
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Development/Plasticity/Repair
The Distinct Temporal Origins of Olfactory Bulb Interneuron Subtypes
Renata Batista-Brito,1,2,4 *
Jennie Close,1,2 *
Robert Machold,1,3 and
Gord Fishell1,2
1Smilow Neuroscience Program and Departments of 2Cell Biology and 3Otolaryngology, New York University Medical Center, New York, New York 10016, and 4Gulbenkian PhD Programme in Biomedicine, Gulbenkian Science Institute, 2781-901 Oeiras, Portugal
Correspondence should be addressed to Gord Fishell, Smilow Neuroscience Program and the Department of Cell Biology, Smilow Research Building, New York University Medical Center, 522 First Avenue, New York, NY 10016. Email: fishell{at}saturn.med.nyu.edu
Olfactory bulb (OB) interneurons are a heterogeneous population produced beginning in embryogenesis and continuing through adulthood. Understanding how this diversity arises will provide insight into how OB microcircuitry is established as well as adult neurogenesis. Particular spatial domains have been shown to contribute specific interneuron subtypes. However, the temporal profile by which OB interneuron subtypes are produced is unknown. Using inducible genetic fate mapping of Dlx1/2 precursors, we analyzed the production of seven OB interneuron subtypes and found that the generation of each subpopulation has a unique temporal signature. Within the glomerular layer, the production of tyrosine hydroxylase-positive interneurons is maximal during early embryogenesis and decreases thereafter. In contrast, the generation of calbindin interneurons is maximal during late embryogenesis and declines postnatally, whereas calretinin (CR) cell production is low during embryogenesis and increases postnatally. Parvalbumin interneurons within the external plexiform layer are produced only perinatally, whereas the generation of 5T4-positive granule cells in the mitral cell layer does not change significantly over time. CR-positive granule cells are not produced at early embryonic time points, but constitute a large percentage of the granule cells born after birth. Blanes cells in contrast are produced in greatest number during embryogenesis. Together we provide the first comprehensive analysis of the temporal generation of OB interneuron subtypes and demonstrate that the timing by which these populations are produced is tightly orchestrated.
Key words: genetic fate mapping; adult stem cells; neuronal birthdate; interneurons; neurogenesis; olfactory bulb
Received Dec. 19, 2007;
revised Jan. 25, 2008;
accepted Feb. 17, 2008.
Correspondence should be addressed to Gord Fishell, Smilow Neuroscience Program and the Department of Cell Biology, Smilow Research Building, New York University Medical Center, 522 First Avenue, New York, NY 10016. Email: fishell{at}saturn.med.nyu.edu
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