Researchers uncover signal needed for blood-brainbarrier harvardmed
Reviewing Editor; University of California, San Diego, United StatesReviewer; University of Wisconsin-Madison, United StatesIn the interests of transparency, eLife includes the editorial decision letter and accompanying author responses. A lightly edited version of the letter sent to the authors after peer review is shown, indicating the most substantive concerns; minor comments are not usually included.
All of the reviewers thought that the work was of potential interest, but that there were a number of major concerns that need to be addressed. The authors convincingly report two apparently independent tracer accumulation modes in the zebrafish larval brain. The first one, previously observed by other investigators, results in diffuse tracer accumulation across the parenchyma, follows near-linear kinetics and, in the context of this study, has been analyzed in the midbrain after at 3 and 5 dpf.
ii) Importantly, avoid any firm causality inferences between BBB phenotypes and at distance tracer accumulation. For instance, in the Abstract the sentence"Electron microscopy studies further reveal that this steady accumulation results from high levels of transcytosis that are eventually suppressed, sealing the BBB" should be rephrased or removed.
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