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Engineered epithelial sheets take a shared orientation once their cells migrate together

Whitehead Institute researchers saw engineered epithelial sheets gain a shared orientation once the cells migrated together, according to a PNAS paper. The experiments used cultured cells, so they show migration can supply the cue and leave open whether embryos use it.

The Scientist · Science desk

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What happened

  • When the engineered cells were induced to migrate collectively, CELSR-containing junctions became enriched along the front-to-back axis.
  • That asymmetry lined up across neighboring cells and kept propagating to the cells behind, turning an unpolarized sheet into one with coordinated polarity.
  • Individual cells interpreted the migration cue directly and stayed responsive to it, which favors direct sensing over relay from a subset of cells.
  • Graduate student Leah Wallach led the paper, working alongside another graduate student, Connor Thomas, and it also points to CELSR, a protein found at cell junctions, as a main driver of how polarity gets started.

Why it matters

  • What's now possible capability Initiation can be followed under fluorescence in cells that start unpolarized, a moment the source describes as hard to catch in animal tissue.
  • Who has to decide decision Researchers choosing which initiating cue to test now have a migration-based candidate to weigh against WNT gradients.
  • Who's exposed exposure Disorders already associated with disrupted planar polarity include spina bifida, craniorachischisis, hearing loss and chronic lung disease, but none was tested in this work.

Li's lab started with engineered cells that had no planar polarity at all. The team labeled proteins involved in establishing polarity with fluorescent tags and followed them over time in cells grown on petri dishes [5]. Any orientation that appeared in the sheet had to emerge during the experiment.

The central observation was an accident, according to the Phys.org account of the paper. The CELSR pattern showed up when the researchers induced the cells to migrate collectively [6]. They then tested two explanations for how a sheet could become coordinated. In one, every cell senses the cue itself. In the other, a subset of cells senses it and relays the information to neighbors [8]. The data favored the first [9].

The section of the write-up that describes the experiments does not include cell counts, the number of repeats or the comparison conditions. Those are the denominators a reader would want before deciding how far the pattern generalizes.

First author Leah Wallach was careful about the protein's role. "We've identified a cue, and we've also found what we think is the protein responsible for actually reading that signal," she said [12]. In our view the qualifier is the right one for a result in engineered cells.

The paper also sits in a field with other candidates. Gradients of WNT proteins have been proposed as guidance signals, and mechanical forces can help maintain or redirect polarity in tissues that are already polarized [10]. The new work addresses the step before that, in a sheet that began unpolarized. Its conclusion is worded as a possibility: collective migration itself could provide the symmetry-disrupting cue [11].

What to watch

  • Whether CELSR enrichment follows collective migration in animal tissue, where growth and shape change run alongside polarity.
  • Cell counts, repeat numbers and comparison conditions in the full PNAS paper.
  • Experiments that pair a migration cue with WNT gradients in the same sheet.

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Evidence55
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Hype gap+15
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  1. [1]

    Researchers in the lab of Whitehead Institute member Pulin Li recreated the emergence of planar polarity in engineered epithelial cells and watched it in real time.

    Reported Supported Source: Phys.orgView cited source
  2. [2]

    The findings, published in the Proceedings of the National Academy of Sciences on Oct. 15, show that collective cell migration provides a cue that establishes coordinated polarity across many cells.

    Reported Supported Source: Phys.orgView cited source
  3. [3]

    The study, led by first author Leah Wallach, a graduate student in the Li lab, in collaboration with graduate student Connor Thomas, also identifies the junctional protein CELSR as a key driver of polarity initiation.

    Reported Supported Source: Phys.orgView cited source

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Sources

1 independent publisher whose own reporting we read for this story.

  1. phys.org

    1 article · October 16, 2026

    Finding their sense of direction: Cell movement helps tissues establish polarity

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