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Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition

ABSTRACT: Organoids can undergo pattern formation by spontaneously forming spatially-localised signaling centers called organisers. Understanding how molecular pathways participate in this regulative process is a central challenge in biology. Here, we investigated self-organisation of a SHH-expressing floorplate in clonal neural tube organoids (NTOs). In NTOs, a pulse of retinoic acid (RA) applied at Day 2 triggers self-organisation of a FOXA2+ floorplate by Day 6. FOXA2 expression was initially spatially scattered before resolving into multiple clusters. These FOXA2+ clusters underwent competition and physical sorting, resulting in a stable “winning” floorplate. We identified BMP signalling as a key governor of long-range cluster competition.

ORGANISM(S): Mus musculus

PROVIDER: GSE236543 | GEO | 2024/04/23

REPOSITORIES: GEO

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Project description:In many animals living in groups the reproductivestatus of individuals is determined by their social status. In specieswith social hierarchies, the death of dominant individuals typicallyupheaves the social hierarchy and provides an opportunity for subordinateindividuals to improve their social status. Such a phenomenon occursin the monogyne form of the fire ant\emph{, Solenopsis invicta, }wherecolonies typically contain a single wingless reproductive queen, thousandsof workers and hundreds of winged non-reproductive virgin queens.Upon the death of the mother queen, many virgin queens shed theirwings and initiate reproductive development instead of departing ona mating flight. Workers progressively execute almost all of themover the following weeks. The workers base their collective decisionon pheromonal cues associated with the onset of reproductive developmentof the virgin queens which occurs after orphaning. To examine the factors that determine which virgin queens are executed and which survive, we set up artificial competitions between queens from different colonies. Using microarrays, we found that queens from winning colonies showed higher mitochondrial as well as organ development activities 24 hours after orphaning than did queens from colonies that lost the competitions. Furthermore, queens from colonies where queens shed their wings faster after orphaning were more likely to survive competitions. Finally, higher wing shedding speed is linked to higher mitochondrial activity. Eight competitions were initially conducted between queens form pairs of colonies. Six competitions clearly identified one winning colony and one losing colony. We thus have microarray data for six competitions (ie biological replicates), with one winning and one losing colony within each competition. Thus 12 colonies total. For each colony, RNA extracted from five queens was pooled, and hybridized against an unrelated common reference RNA that had been made from a pool of many S. invicta individuals of all castes and developmental stages. Lab work was conducted in blocks (by competition) with randomized order within competition to avoid introducing bias. No technical replication was performed.

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Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster competition

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