How do complex tissue shapes influence organ functions?

Sneha Singhal, Jaypee Institute of information technology, Noida

We are made up of tissues arranged in complex shapes that aid in the functions of our bodies, ranging from the smooth tubes of our arteries and veins to the textured pockets of our internal organs. When cells are folding into such complicated configurations, how are they able to do so so precisely? How do these processes work?

The Recent Study:

Now, Harvard Medical School researchers have found a mechanical method through which sheets of cells transform into the inner ear’s tiny, looping semicircular canals. The study, which was conducted in zebrafish, found that the process requires a combination of hyaluronic acid, which is produced by cells and swells when exposed to water, and thin connectors between cells that guide the force of this swelling to form the tissue. Despite being conducted in zebrafish, the research discloses a basic mechanism for how tissues take on shapes—one that is likely to be conserved throughout vertebrates and could have consequences for bioengineering, according to the researchers.

Transparency Model:

Sean Megason, senior author of the paper and a professor of systems biology at HMS’ Blavatnik Institute, and his colleagues investigate how cells evolve into complex three-dimensional structures. They used a classic—and ideal—model organism, the zebrafish, to answer this question. Akankshi Munjal, who worked on the research while a postdoctoral researcher at HMS before becoming an assistant professor at Duke University, explained the process in her own words. The semicircular canals, three fluid-filled tubes in the inner ear that are required for balance and spatial orientation, are among these components. Because the semicircular canals are hidden by the middle and outer ear in many species, little is known about how they originate.

Researchers can observe the development of zebrafish’ canals under a microscope because they are located close to the surface. As Munjal explained, it was interesting watching the formation of three-dimensional organs from single sheets of cells. Megason continued, “With complete access, we could examine the inner ear in the embryo”. He explained, “It’s a metaphor for how complex structures are created from cells working together in the embryo”. “We went in thinking it would be a lovely structure, but we had no idea what we’d find.”

Their findings surprised them:

The proteins actin and myosin are thought to work as small motors inside cells, pushing and tugging the tissue in different directions to fold into a specific form. The researchers observed, however, that zebrafish’s semicircular canals are formed in a very distinct way. The cells create hyaluronic acid throughout development, which is well known as an anti-wrinkle ingredient in cosmetics. The acid swells up once it enters the extracellular matrix, similar to a diaper in a swimming pool. The swelling generates enough force to physically move surrounding cells, but because the pressure is uniform in all directions. The researchers were puzzled as to why the tissue stretches in one direction but not the other to form an elongated shape. The scientists discovered that this is performed through cytocinches, which are narrow connectors between cells that constrain the force.

Munjal described it as “like putting a corset on a water balloon and deforming it into an oblong structure”. A flat sheet of cells is gradually shaped into tubes by a combination of swelling and cinching. “Our work demonstrates a novel method of accomplishing things,” Megason said. He added that he hopes it will prompt people to think about other mechanisms that may be involved in tissue sculpting. Actin and myosin act at the molecular level, and pressure describes the more physical approach. Only time will tell how effectively the two forces work together.”  Their discovery is expected to have far-reaching repercussions. Megason and Munjal have been added to the mix.

Evolutionary implication of the findings:

The genes that regulate hyaluronic acid production in zebrafish semicircular canals are also found in mammalian semicircular canals. This implies that a comparable process takes place in both species. In addition, hyaluronic acid may play a crucial role in the shape of various tissues and organs, as it is found in numerous areas of the body, including the skin and joints. If this is the case, researchers may be able to better understand congenital disorders in organs where hyaluronic acid drives development by researching the genes involved in hyaluronic acid production. Munjal believes that “this is likely to be a broad, conserved process across species and organs.”

The process could be used in bioengineering, where scientists are aiming to prod stem cells into producing buds, tubes, and other complex forms to cultivate organs in the lab. Megason acknowledged that lab-grown organs are still a work in progress, but that understanding how organs form inside an organism is a critical first step. Megason explained, “We’re trying to unravel the steps of how a complicated organ like the inner ear is formed in vivo and then quantify those steps.” “We’re hoping that this will lay the framework for cells to develop in whatever pattern or shape we wish.”

Also read: Chewing gum can reduce the risk of oral virus transmission of SARS-CoV-2!

Reference:

Munjal, A., Hannezo, E., Tsai, T. Y.-C., Mitchison, T. J., & Megason, S. G. (2021). Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis. Cell, 184(26), 6313-6325.e18. https://doi.org/10.1016/j.cell.2021.11.025

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Author info:

Sneha Singhal is currently pursuing B.Tech in Biotechnology from Jaypee institute of information technology, Noida. She has a keen interest in research in bioinformatics and Genetics. She aspires to be a researcher in upcoming time.

LinkedIn: www.linkedin.com/in/sneha-singhal

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