The graphical abstract from the paper visually contrasts a mutant versus non-mutant pathway: a genetic variant upregulates conversion of retinal into ATDR and then ATDRA, and this signal reaches OPCs (the green precursor cells), pushing them to mature and wrap axons in new myelin. Without enough ATDRA signal, OPCs fail to complete that transition and myelin stays damaged. The abstract also includes a Morris water maze test showing mutant mice navigating to a target far faster than wild-type mice, reflecting preserved cognitive function tied to myelin repair.
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Researchers used genetic engineering to express the mutation selectively in neurons only, rather than in oligodendrocytes, to prove the signal originates in neurons.
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The bottom of the graphical abstract shows two blue circles representing wild-type versus mutant mice performing the Morris water maze, with the mutant reaching the target markedly faster.
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1:24:09>> All right. And so now we can finally understand the graphical abstract. We're finally here. >> Okay. >> The wild type is on the left. The mutation is on the right. You've got a Himalayas in the background. Um retinol goes to ATDR goes to ATDR. But on the right hand side, the ATDR has an up arrow >> because it's upregulated. That's that gain of function. >> And when that goes to the OPC's and the oligodendritty, >> the OPC's are the green cells. >> When it goes to the OPC's, it creates myelin around my axon. On the left hand side though, there's not enough signal.
1:24:49>> Mhm. >> To get the OPC's, those stem cells to become myelin. >> Okay. And so on the right hand side, we're getting healthy myelin. On the left hand side, we are not >> not. Yeah. Yeah. >> And that's the graphical abstract. Yes, that's and and we from something that was totally disconnected from anything you'd be able to to understand. We we now have a reference point and also like a fundamental understanding of one of the most uh you know uh impactful neurodeenerative you know issues we we face as humanity among others. among others. Yeah, which we've discussed. >> I mean, >> any any progress is good progress, right? And on the bottom, the the the
1:25:29two blue circles on the left hand side, you see a wild type mouse just doing random walks to get to the cheese, the Morse water maze. On the on the right hand side, >> it's getting there very very quickly >> because it's able to repair itself and maintain its cognitive functions. >> Very good. >> Uh in a way that the the wild type cannot. >> There it Oh, the the bio stories some of our best stories. >> Yeah. I mean, I just it's it's incredibly difficult. >> Yeah. >> To get this kind of granular >> understanding Yes. >> of something so fundamental. And it's just very cool the amount of technology that we have in order to do this. Like
1:26:09so much had to like we know how to we we know how to stain myelin extremely well. We know how to make these um mouse assays with any type of genetic mutation that we want. Not only that, we know how to express only that genetic mutation in neurons only or oligodendrites only, right? In order to establish it's not the oligodendrites, it's only it's the neurons that are doing this. We had to express that gene in only the neurons, which is kind of crazy. And and the way they do it is with like this kind of thing that the neuron creates a type of protein and then that protein is going to go in and trigger. Yeah, it's I mean incredible amounts of
1:26:51genetic engineering, bioengineering to get this kind of access, you know, and also just it's just standard like scientific method. >> It's one would say they uh did it from first principles. >> It one would say that I certainly would
Evolutionary BiologyNeurobiologyPharmacologyRegenerative Medicine