At the origin of the tubes...
Jan. 20, 2013
An IGBMC team has uncovered the mechanism controlling how biological tubes form. Their data suggest that their conclusions could be valid in humans and lead to a better understanding as to how the lymphatic system is generated. The results are published on 20 January 2013 in the journal Nature Cell Biology.
Using a simple model to explain a complex process
Caenorhabditis elegans is a 1 mm long worm made of less than 1000 cells. Among them one cell, known as the excretory cell, forms four connected tubules which help the animal to maintain its water balance. Unlike more complex organisms, C. elegans tubes are unicellular, which greatly facilitates their study. The worm is widely studied amongst the scientific community to observe basic biological mechanisms that are, most often, conserved in humans.
Tube development, step by step
The researchers used electron tomography in order to observe the genesis of these tubules at a nanometric scale (10-9 m). Through a "slice by slice" analysis, this method allowed the team to reconstruct the inner volume of the cell, thereby showing that the lumen (the inner space of the tube) extends when vesicles coalesce with the pre-existing lumen. The latter are filled up with ions, and the pressure makes them fuse with the lumen, which feeds it with new membrane and creates pressure on its extremity. Intermediate filaments surrounding the lumen provide an outside "network" whose role is essential in maintaining the tubule integrity.
Key role of PROS-1 at a molecular level
Michel Labouesse’s team also demonstrated that the transcription factor PROS-1 is a key player in controlling tubule formation and growth. In particular, PROS-1 regulates the expression of genes responding to osmotic stress, controlling the process of vesicle fusion with the membrane or guiding lumen outgrowth such as the aforementioned intermediate filament-coding gene.
Toward new therapies?
Renal tubules, bronchial tubes, lymphatic vessels… Tubular networks are ubiquitous amongst the living matter and many disorders, as lymphoedema or even cancer, affect their development or function. A better understanding of the development of these tubes is therefore crucial to develop new therapies. Interestingly, PROS-1 transcription factor, whose importance has been demonstrated in this study, has a homologue in vertebrates: Prox1, which is known for its role in the formation of the lymphatic system. Therefore, it is likely that the results obtained in C. elegans can at least partly be extended to humans. These are promising news, raising hopes to treat disorders affecting the lymphatic system.