New insights into cellular ‘bridges’ shed light on development and disease – ScienceDaily


Most cells in the bodies of living organisms repeat their contents and divide physically into new cells through the process of cell division. But in many species, the germ cells, which become eggs or sperm, don’t separate completely. They remain interconnected by small bridges called annular ducts and clump together.

In a new study, Yale researchers have discovered for the first time how germ cells in fruit flies form these ring ducts, a discovery they say will provide new insights into a feature widely shared in development and in diseases in which cell division is disrupted.

The results were published March 9 in developmental cell.

Scientists have observed ring ducts in male and female germ cells in all kinds of species, from simpler organisms such as sponges and fruit flies to more complex animals such as mice and humans. And although their purpose is not fully understood, there is evidence that the annular ducts are important for cell development, the researchers say.

“For example, in female fruit flies, the annular ducts are required for the development of a functional oocyte, which is a developing egg cell,” said Lynn Cooley, CNH Long Professor of Genetics at Yale University School of Medicine and senior author of the new study. “If you block the annular ducts, the female flies develop tiny, tiny eggs and cannot reproduce.”

But how the annular canals formed remained unclear.

To better understand their formation, the researchers used a live imaging approach. They labeled several ring duct proteins in fruit flies with fluorescent particles and, using a microscope, observed what these proteins did over time in the germ cells of both males and females.

“When we did that, we saw the first signs of a structure we call the germinal midline,” said Carrie Price, a postdoctoral fellow in the Cooley lab and lead author of the study.

The midbody is a structure that forms during cell division and one of its roles is to recruit molecules needed to cut cells at the end of the process. In the study, the researchers found that an unusually large mesangial body formed in the germ cells of a fruit fly remained stuck for 20 to 30 minutes, and then, instead of initiating full separation, underwent a radical reconfiguration from ball to ring. These midbody loops then became stable annular channels connecting sister cells.

The researchers also found this transition of the channel from the midbody to the annulus in polyps and freshwater mice, suggesting that it is a feature that has been conserved throughout evolution.

“To see this small, solid body turn into a ring — it hadn’t been observed in healthy, living cells before. It was absolutely amazing to us; it was an ‘a-ha’ moment,” Cooley said. “And it would have been hard to detect this in anything else. other than fruit flies. This study is a great example of how model systems such as fruit flies are essential to understanding the underlying mechanisms of development.”

In addition to being an important step toward understanding the function and formation of the annular ducts, the researchers say, the new finding may also give insight into the incomplete cell division that occurs in typical development across a variety of species and in diseases in which incomplete cell division is present. Implicated, such as colorectal cancer, Hodgkin’s lymphoma, and some immunodeficiency syndromes.

The findings may also help scientists understand the beginnings of evolution.

“There are very primitive organisms that, when they divide, make colonies that are connected by fixed cell bridges, much like what we see with germ cells,” Cooley said. “This way of keeping sister cells connected in a colony or cluster is probably the beginning of how multicellular evolution happens, and germ cells are probably a reflection of that.”

Moving forward, the researchers aim to identify the mechanisms that drive germ cells to stay attached.

“In this current study, we saw that blocking an enzyme called citron kinase delays or prevents the transition of the duct from the midbody into the loop,” Price said. “So we’re looking at Citron kinase more deeply to see what exactly it does in these cells during division.”


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