Identification of a mechanism to explain the reorganisation of microtubules into an array that is key to the morphogenesis of a tubular organ
Laser-ablation of microtubules (in green) in cells leads to fast recruitment of the protein Patronin (in magenta) to newly formed microtubule minus ends.
Organ development during embryogenesis in most animals requires the transformation of simple sheets of cells into complex 3D structures. Organ shape, and therefore functionality, is ultimately determined by the arrangement of cells within the organ, and the shape of these individual cells. Although the cytoskeleton is known to play an important role in determining cell shape, how components of the cytoskeleton become organised into specific arrangements has remained unclear. Now, Katja Röper’s group, in the LMB’s Cell Biology Division, has shown the mechanism by which microtubules are re-organised to allow cell shape change during tubular organ formation.
This study was led by Ghislain Gillard, a postdoc in Katja’s group, who analysed the budding of the epithelial tubes in the salivary glands of Drosophila melanogaster (fruit fly) embryos. Epithelia are layers of cells that form a lining, such as the outermost layer of skin or the inner linings of tubes throughout the body, such as blood vessels, airways, and intestines. With so many parts of the human body formed from tubes, the study of salivary glands in fruit flies can shed crucial insight onto human organ development.
To transform a flat sheet of cells into a tube, cells go through a process called apical constriction in which the apical side of the cell, which is the side that will face the inside of the tube, is made narrower, so that the cells become more wedge-shaped. As the layer of cells are all tightly connected, this can create a bend in the sheet and start the process of tube formation: just as square bricks build a wall, whereas wedge-shaped bricks will create an arch. Previous work from Katja’s group had demonstrated that this process depended on a specific arrangement of microtubules, but it was unclear how they became organised in this way.
Microtubules are often formed at an organelle called the centrosome. Katja’s group discovered that, after the last embryonic division cycle of the epithelial cells of the salivary gland, two proteins, Katanin and Patronin, accumulate at the apical end of the cell, where the microtubules are severed from the centrosome by the protein Katanin. These released microtubules are then quickly captured by Patronin. Patronin anchors one specific end of the released microtubules at the apical part of the cell, so that they point towards the opposite end of the cell on the outside of the tube. This process, known as a release-and-capture mechanism, as Katanin releases the microtubules from the centrosome and Patronin then captures them, then allows the apical constriction of the cell that drives tube formation.
This study has shed important insight into a fundamental process of biology. As most of our own internal organs are tubular in nature, any insights into the formation of these organs will inform a better understanding of developmental disorders such as Spina Bifida or Polycystic Kidney Disease. Additionally, knowledge of these fundamental processes could also be applied to inform tissue engineering attempts in the future.
This work was funded by UKRI MRC.
Further References
A release-and-capture mechanism generates an essential non-centrosomal microtubule array during tube budding. Gillard, G., Girdler, G., Röper, K. Nature Communications, 12, 4096.
Katja’s group page
Previous Insight on Research
How flat sheets of cells become tubular organs: observing cellular dynamics from 2D to 3D