Research highlights: Morphogenesis

I would like to describe two excellent talks given at BPS 2018, both on tissue morphogenesis, that were not printed in the BPS 2018 abstracts publication. It would be a shame if they didn’t get the exposure they deserve. (Disclaimer: this summary and any possible inaccuracies are entirely my own.)

1) Sevan Hopyan gave a talk entitled “Volumetric Morphogenesis in the Mouse Embryo” in the Mechanobiology subgroup on Saturday. The Hopyan lab studies how cell rearrangements remodel epithelia, and the talk focused specifically on the mandibular arch in the developing mouse. In a short, four-hour period, this arch morphs from a small, bud-like protrusion to a larger bulbous protrusion with a narrow neck. 

How does this simultaneous expansion of the distal region and narrowing of the neck region occur? They thought at first that directed dilation of cells explained it entirely. It turns out, however, that changes in physical properties and cell division are insufficient to explain the tissue’s shape. In the mandibular arch, mesenchymal cells are actually so dense that they appear similar to an epithelial sheet. The researchers asked whether mesenchymal cells crawl forward or simply exchange neighbors (intercalate) to remodel the tissue.

The researchers found that a particular type of neighbor-exchange occurs (termed T1) and that this exchange could help drive the morphogenesis of the arch. They modeled these cells in analogy to bubbles in a foam and asked what kinds of energy changes might correspond with the neighbor-exchanges they observe, following prior work by Lisa Manning’s group. Particularly interesting was the shape fluctuations observed in the cells, which may help bump cells over the energy barrier that prevents them from exchanging neighbors.

They then went on to explore molecular mechanisms underlying this process, making use of in vivo tension sensors designed by Carsten Grashoff to probe the forces experienced by the adhesion protein, vinculin. The importance of Ca+ signaling through mechanosensitive ion channels was also highlighted in their results.

2) The second talk I would like to highlight was given by Ron Vale at the Cytoskeleton Symposium on Tuesday, entitled “How the intestine got its stripes.” Ron very graciously stepped in for a speaker who was, unfortunately, not able to make it. He started by asking the broad question: What governs the patterning of cells? The answer, he promised, would in fact involve the cytoskeleton.

To answer this question, Kara McKinley (postdoc in the Vale lab) used in vitro intestinal organoids. She made two initial observations: First, during mitosis, the dividing cell first rounds up and thereby moves closer to the apical surface (the one near the inside of the gut). Second, cell divisions appeared to generate an alternating protein expression pattern because the two daughter cells would move away from each other rather than remaining neighbors.

They found that mitotic rounding toward the apical surface was dependent on the actin cytoskeleton but not microtubules. This result, they believe, is consistent with how epithelial cells anchor themselves to the apical surface via adherens junctions, adhesions that connect primarily to the actin cytoskeleton.

To determine how daughter cells separate, they paid particular attention to the shape of the cytokinetic furrow. What they saw was that dividing cells only furrow from the basal surface, such that during cytokinesis, an outline of the two cells would appear similar to a cartoon heart shape (but without the pointy part). This basal gap allows a neighbor cell to insert itself between the two daughters.

Because the neighbor cell that is inserting into the gap must migrate over one of the daughter cells, the researchers asked whether the height difference between the mitotic cell and its neighbors could regulate this interspersion. In a collaboration with Loic Royer, they modeled cells as Brownian spheres and found that the height difference between mitotic cells and neighbor cells could plausibly determine whether daughter cells dispersed or remained in isolated groups.

This finding appeared to be confirmed by biological experiments and observations. For example, Wnt signaling that promotes a shorter, more cuboidal morphology also results in clonal patches rather interspersed patterns. Fetal organoids are also cuboidal and rarely exhibit neighbor insertions. The results from the Vale lab therefore shed light on the importance of physical parameters in determining tissue patterning.


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