The signals that cause cells to self-destruct

The signals that cause cells to self-destruct

CVM cells (in red) trace along a path made of TVM cells (green). The TVM cells send a signal, letting the CVM cells know they are going in the right direction. CVM cells are approaching a juncture in the embryo where they will encounter high (blue) BMP signals, which would indicate that the CVM needs to replicate itself and proliferate. BMP signaling also triggers the release of expression of a ‘toxic’ gene, called hid, and unless proliferating cells closely adhere to the TVM pathway, hidding will kill them. In this way, the developing embryo performs quality control, ensuring that any stray cells are eliminated. Credit: F. Macabenta

Most human hearts look almost identical – muscle cells in the same places, vascular structures in the same directions. Organs like hearts or stomachs look alike and function the same across individual organisms in a species because cells follow rigorous processes during development that put them exactly where they need to go.

The development process includes countless steps that must occur in a precise order and style. Studying these complex steps is the focus of the lab of Angela Statopoulos, a professor of biology at the California Institute of Technology. The lab uses fruit flies, which have a 24-hour growth cycle with noticeable changes that can be observed nearly every minute, as a model system.

A new paper from the Stathopoulos lab examines caudal visceral mesoderm (CVM) cells, which will eventually become muscle fibers in the intestines of Drosophila. These cells migrate from the back of the developing embryo to the front over a period of six hours—the longest migratory distance of all stages of Drosophila embryonic development.

The new research identifies the mechanisms that ensure that any stray, wandering cells will self-destruct through a particular form of cell death It is called anoikis. Interestingly, resistance to anoikis is a precursor to many types of metastatic cancers. Understanding the pathways that direct healthy anoikis may eventually provide insight into how cancers spread and why they invade certain parts of the body.

“Cell death is a normal, healthy part of development,” Statopoulos says. “A migratory cell must constantly make decisions and find out if it is in the right place in the body. If it is not in the right place, it needs to self-destruct. We have now identified the pathways through which a cell can do this.”

CVM cells (white) migrate around a bend in the embryo. When they make this transformation, they begin to multiply and multiply. Credit: F. Macabenta

The paper appears online in the journal developmental cell On June 15. Frank Macapienta, a senior postdoctoral research associate in biology and biological engineering at Caltech, is the study’s first author.

CVM cells do not make their long journey through the Drosophila embryo alone. These 40 to 50 cells follow a pathway that is made up of a different type of cell called the stem visceral mesoderm (TVM). TVM cells release a chemical signal called fibroblast growth factor (FGF), which lets the CVM cell know it is in the right place.

In the middle of their migration, CVM cells should travel around a sharp curve in the embryo, which is roughly U-shaped. At this juncture, CVM cells begin to multiply expecting to be near the end of their journey, when it is time to start building muscle. The problem is that as the cells begin to multiply, some of them begin to deviate from the TVM pathway. The researchers previously noted that this is the point at which these missing cells will undergo anoikis and self-destruction.

A gene called hid (short for head reversion defect) is responsible for anoikis. When hid is expressed in a cell, the cell dies. In the new work, Macabenta found that CVM cells begin to express burrow as they spin around a bend in the embryo, but do not die—unless they fall from the TVM pathway.

The team found that this is possible thanks to FGF signaling, which acts as a hiding antidote: if a cell falls off the path and thus stops receiving FGF signals, it will die; He can survive even though he’s in hiding as long as he stays on the right track. In this way, the fetus can be assured that any stray cells will self-destruct, while properly functioning cells are preserved.

الإشارات التي تجعل الخلايا تدمر نفسها بنفسها

Graphic summary. attributed to him: developmental cell (2022). DOI: 10.1016/j.devcel.2022.05.017

Finally, the team also discovered that a specific pathway, called the bone-forming protein (BMP) pathway, controls the timing of the initiation of cell proliferation. BMP signaling begins just as cells navigate in the U-shaped juncture, approximately midway through their migration. This is the signal that allows cells to divide and grow in number.

Cells have an internal “clock”, known as the cell cycle, that controls the timing of growth, DNA replication, and cell division (mitosis). The team found that the timing of hid expression is linked to cell cycle progression, and when this is disrupted, hid is not expressed at the correct point during cell migration. BMP signaling is essential to allow the cell cycle to move forward equidistant It is thus also essential for the precise timing of hid expression, because cells that fail to divide cannot express hid in time to eliminate the missing cells.

It is critical for cells to be able to possess these programmed quality control mechanisms because stray cells can destroy the proper development of the rest of the organism.

“When we removed the hiding gene, the cells that got off track would survive and eventually invade and disrupt the central nervous system, where they really shouldn’t be,” Macapienta says. “They’re not on the right track anymore, so they’re back in a kind of ‘Plan B’ where they find a site that they have some affinity for. If you look at the autopsies of people who have had metastases. cancer, usually the migrated cells travel to specific locations. Our research serves as a system that we hope to understand how this works, and how cells skew and detect “second best” signals to follow. In future work, we would like to see what other signals or signals for CVM cells They follow it leads them to the central nervous system. This could explain why certain types of metastases prefer to colonize other tissues.”

A new study reveals how a human fetus develops the precursor of hematopoietic stem cells

more information:
Frank Macapienta et al, driving BMP-gated cell cycle progression anoikis during mesenchymal mass migration, developmental cell (2022). DOI: 10.1016/j.devcel.2022.05.017

the quote: Signals that make cells self-destruct (2022, June 15) Retrieved June 15, 2022 from

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