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Ali Erturk @erturklab
, 12 tweets, 6 min read Read on Twitter
I am excited to share our publication of vDISCO technology: a whole mouse body clearing & imaging method nature.com/articles/s4159…. The thread below presents details of vDISCO and its biological findings. @NatureNeuro @nature. Happy New Year all! 1/12
2 years ago, we published uDISCO to clear and image intact adult mouse body with light-sheet microscopy. However, neuronal details were mostly invisible through intact bones, skin and highly autofluorescent muscles. nature.com/articles/nmeth…. 2/12
Now, we developed the vDISCO technology to overcome these problems, and generated a clear whole mouse neuronal projection map of the Thy1-GFPM mouse. 3/12
So, how does vDISCO work? We use nanobodies to immunolabel fluorescent proteins in whole mouse body. These nanobodies are conjugated to bright far-red Atto dyes, which then stabilize and amplify the signal of fluorescent proteins. 4/12
I hear you asking "but we usually clear only organs, not whole mice. Can we use the vDISCO for organs?" Well, yes, indeed we also use vDISCO for almost all our single organ experiments as it both amplifies the signal ~100 times and stabilizes it for good. 5/12
So, what did we learn using vDISCO? We studied whole nervous system after brain trauma using vDISCO. We found that TBI leads degeneration of peripheral nerves, which can explain the diverse chronic symptoms of TBI, including sensory & motor dysfunctions. 6/12
Next, we used vDISCO to study meningeal vessels, based on works of @jonykipnis, Nedergaard, Alitalo and others. Doing so, we serendipitously found that there are short vascular connections between meninges and skull marrow, which we named skull-meninges connections (SMCs). 7/12
Well, clearly we are not the only one to report these connections. Just a few months back, @MatthiasNahrend group also reported at Nature Neuroscience similar connections (ncbi.nlm.nih.gov/pubmed/30150661). 8/12
Using vDISCO, we showed that these connections are filled with immune cells upon stroke, particularly with neutrophils as also observed by Nahrendorf team. 9/12
What would be translational implications of these skull-meninges connections? Are they involved in brain function in physiological conditions and/or during pathologies? Are they related to meningeal lymphatics? A lot of exciting research is ahead. 10/12
We presented vDISCO recently at @FENSorg @SfNtweets and @czbiohub. If you missed them check out our manuscript and discotechnologies.org for more details and tips. 11/12
Finally, do you want to establish the vDISCO in your lab? Very easy!!! Check out our workshop videos at discotechnologies.org/workshop, and email us if you have questions. You can also join our annual workshop! 12/12
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