A scientific study made by the researchers Francesc Cebrià, Sara Barberán and Susanna Fraguas, from the Department of Genetics, Microbiology and Statistics of the Institute of Biomedicine of the University of Barcelona (IBUB), based at PCB, describes for the first time the function of a signalling pathway –particularly, the pathway of epidermal growth factor receptors (EGFR) - in the differentiation of the planarian digestive lineage. EGFR pathway, evolutionarily preserved, has a fundamental role when regulating the cell differentiation and proliferation in lots of organisms (such as mammals’ neural stem cells) and it is over-activated in most of human cancers. 

The planarian Schmidtea mediterranea is an invertebrate used as a model in studies for genetics of development and biomedical research. It shows a great regenerative ability, based on pluripotent adult stem cells –neoblasts- which are maintained over all the life cycle of the organism, and is an exceptional model to study the behaviour of these stem cells in vivo in regenerative processes of an animal using a small part of it. In regenerative medicine, research with planarians could promote the design of future therapies based on stem cell transplant or differentiated cells taken from stem cells in patients affected by neurodegenerative illnesses (Parkinson, Alzheimer, etc.), diabetes or cardiac pathologies.

According to Professor Francesc Cebrià, who directed this scientific project –published in an article of the distinguished magazine Development (doi: 10.1242/dev.131995)––, “the neoblasts, which are the only cells with ability to be divided, are necessary for the renewal of cells that die in the physiologic usual renewal or tissue homeostasis. When we cut a planaria, neoblasts are equally needed to regenerate tissues and amputated organs”.

“We still do not know how these progenitors end up differentiating from the several cell types” says Cebrià. “In most of the cases, we do not know the signalling pathways or genetic programs regulating this final differentiation of the different cell types coming from their progenitors. It is known from long ago that neoblasts are not a homogeneous cell population: some show specific transcription factors which derive to particular lineages. That means they are no longer pluripotent neoblasts but specialized progenitors: for example, progenitors shown by the transcription factors sim or coe, give place to particular neural types, and it has been postulated that progenitors expressing hnf4 or gata4/5/6 would give place to digestive cells”.
 

EGFR pathway: revealing enigmas about cell differentiation

Since the discovery of the epidermal growth factors (EGF) in 1962, isolated by Stanley Cohen (Nobel Prize in Medicine 1986), the route of epidermal growth factor receptors (EGFR) has been linked to cell proliferation processes, cancer and designs for new oncology therapies. Previous planaria studies suggest that the EGFR pathway could regulate the differentiation of different cell types (pigment cells in eyes, pharynx, excretory cells or different neural types, etc.). However, there is still no definite evidence and there are lots of unanswered enigmas about the mechanisms of differentiation of different progenitor cells on specific cell types.

This is the first scientific study that shows the fundamental role of the EGFRs pathway in the final differentiation of a particular cell type: in this case, the digestive system cells. In order to have the results, the experts have combined RNA interference experiments to silence the function of genes and markers with ethinil-deoxyuridine (EdU) to know the final destiny of the cells coming from the neoblasts.
 

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