Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids

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dc.citation.articleNumber497en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber13en_US
dc.contributor.authorLiu, Lizhongen_US
dc.contributor.authorNemashkalo, Anastasiiaen_US
dc.contributor.authorRezende, Luisaen_US
dc.contributor.authorJung, Ji Yoonen_US
dc.contributor.authorChhabra, Sapnaen_US
dc.contributor.authorGuerra, M. Ceciliaen_US
dc.contributor.authorHeemskerk, Idseen_US
dc.contributor.authorWarmflash, Aryehen_US
dc.date.accessioned2022-03-24T13:31:48Zen_US
dc.date.available2022-03-24T13:31:48Zen_US
dc.date.issued2022en_US
dc.description.abstractMorphogens are signaling molecules that convey positional information and dictate cell fates during development. Although ectopic expression in model organisms suggests that morphogen gradients form through diffusion, little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis due to the combined difficulties of measuring endogenous morphogen levels and observing development in utero. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells, during specification of germ layers. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a paradigm for tissue patterning by an activator-inhibitor pair.en_US
dc.identifier.citationLiu, Lizhong, Nemashkalo, Anastasiia, Rezende, Luisa, et al.. "Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids." <i>Nature Communications,</i> 13, (2022) Springer Nature: https://doi.org/10.1038/s41467-022-28149-3.en_US
dc.identifier.digitals41467-022-28149-3en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-022-28149-3en_US
dc.identifier.urihttps://hdl.handle.net/1911/112059en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleNodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloidsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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