Cell Division Lab. IRB Barcelona & ICREA. The Barcelona Institute of Science and Technology

PRESS RELEASE

Ewing sarcoma is the second most frequent bone tumour in children, adolescents, and young adults. There is no specific treatment for this disease and current management is still limited to surgery, radiotherapy, and chemotherapy. The long-term survival of patients with metastatic or relapsed Ewing sarcoma is very low.

Ewing sarcoma is caused by a single oncogene that results from the fusion of two genes. Although a variety of genes may be involved, EWSR1 and FLI1 and the resulting cancer-driving oncogene, known as EWS-FLI, are found to be responsible in the majority of patients. Unlike most other types of cancer, all attempts to develop experimental animal models of Ewing sarcoma in mice (expressing the EWS-FLI oncogene) have failed.

Prompted by the need for a genetically tractable model that could be used to study the disease, researchers led by Dr. Cayetano González, ICREA research professor at IRB Barcelona, and Dr. Jaume Mora, scientific director at the IRSJD Pediatric Cancer Center Barcelona (PCCB), have engineered Drosophila transgenic strains that express a mutant variant of the human oncogene called EWS-FLIFS. Remarkably, they have found that expression of the human EWS-FLIFS protein in certain types of Drosophila cells triggers the same oncogenic pathways known to account for EWS-FLI oncogenic activity in human patients.

PRESS RELEASE

This study focuses on a type of neuronal cilia, the structures that by sensing chemicals and mechanical forces allow for smelling, hearing, and many other essential functions. 

Many cells in our bodies present a small structure that looks like, and as a matter of fact works as an antenna, conveying to the cell information on the extracellular environment. They are called cilia (plural) or cilium (singular). Ciliated cells play essential functions in the human body. Thus, for instance, the monitoring of fluid flow in the kidney, the detection of hormones in the brain, or the senses of hearing and smell depend on specialised neurons equipped with chemo-sensory or mechano-sensory cilia. Moreover, besides sensing, beating cilia keep fluids in motion in many parts of our bodies and are critical for human health. 

A cilium can be regarded as a long and thin protrusion of the cell membrane that contains microtubules. Ciliary microtubules are arranged in a typical radial symmetry that is conserved through evolution and is templated by a small organelle that sits at the base of the cilium, known as basal body. Most animal cells contain two basal body-like structures (centrioles), but only one of them can actually work as basal body. In human cells, this is always the centriole that is said to be the "mother" (red dot in this image) because it was assembled earlier than the other, called the "daughter" centriole (green dot in this image).

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The study, published in The Journal of Cell Biology, focuses on the development of the sperm tail, the structure that enables sperm cells to swim and is therefore critical for male fertility.

In flies, as in humans, the sperm cell (spermatozoon) is made of the cell body proper, which is also referred to as the sperm “head”, and the flagellum. The flagellum, also known as the sperm “tail”, is a slender lash-like appendage that protrudes from the cell body. It is by beating their tails that sperm cells can swim to reach and fertilise the female reproductive cell (oocyte). A bundle of microtubules that span the entire length of the tail is critical for flagellar beating. These microtubules are arranged in a characteristic radial symmetry that is conserved through evolution and is templated by a small organelle that sits at the base of the flagellum, known as basal body.

Using the vinegar fly Drosophila melanogaster as an animal model to investigate how the sperm tail develops we found that CENTROBIN plays a critical role in the assembly of a subset of microtubules within basal bodies. In the absence of CENTROBIN, basal bodies lack these microtubules and so do the tails that they template that are not motile. Consequently, CENTROBIN mutant males are sterile.