Abstract
The behavior of adult-born cells can be easily monitored in cell culture or in lower model organisms, but longitudinal observation of individual mammalian adult-born cells in their native microenvironment still proves to be a challenge. Here we have established an approach named optical cell positioning system for long-term in vivo single-cell tracking, which integrates red-green-blue cell labeling with repeated angiography. By combining this approach with in vivo two-photon imaging technique, we characterized the in vivo migration patterns of adult-born neurons in the olfactory bulb. In contrast to the traditional view of mere radial migration of adult-born cells within the bulb, we found that juxtaglomerular cells switch from radial migration to long distance lateral migration upon arrival in their destination layer. This unique long-distance lateral migration has characteristic temporal (stop-and-go) and spatial (migratory, unidirectional or multidirectional) patterns, with a clear cell age-dependent decrease in the migration speed. The active migration of adult-born cells coincides with the time period of initial fate determination and is likely to impact on the integration sites of adult-born cells, their odor responsiveness, as well as their survival rate.
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Acknowledgements
We thank E Zirdum, A Weible, G Heck and K Schoentag for technical assistance; F Gage for the retroviral vector backbone; J Nabekura for his advice on naris closure protocols, and V H Perry and J Sheng for valuable comments on the manuscript. This work was funded by fortüne-Programm of Tübingen University, Nr. 2175-0-0. KR and BF have been supported by SFB841.
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( Supplementary information is linked to the online version of the paper on the Cell Research website.)
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Supplementary information, Figure S1
Building up the oCPS. (PDF 166 kb)
Supplementary information, Figure S2
A three-dimensional view on the migration traces of olfactory bulb interneurons within a sample field of view (PDF 112 kb)
Supplementary information, Figure S3
An example migration trace of an adult-born JGN and comparison of methods categorizing the migration mode. (PDF 191 kb)
Supplementary information, Figure S4
The effect of naris closure on migration properties of adultborn JGNs in the glomerular layer. (PDF 282 kb)
Supplementary information, Figure S5
Distribution of migration steps of juxtaglomerular neurons. (PDF 107 kb)
Supplementary information, Data S1
Supplementary methods. (PDF 65 kb)
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Liang, Y., Li, K., Riecken, K. et al. Long-term in vivo single-cell tracking reveals the switch of migration patterns in adult-born juxtaglomerular cells of the mouse olfactory bulb. Cell Res 26, 805–821 (2016). https://doi.org/10.1038/cr.2016.55
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DOI: https://doi.org/10.1038/cr.2016.55
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