Organ regeneration and cellular plasticity

Developmental Molecular Biology
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)

One of the most exciting challenges in biology is to understand how an organism can replace missing organs after damage. This capacity, known as regeneration, differs greatly across organs and organisms, and includes a wide range of phenomena, from wound healing to the induction of regenerative growth to reconstruct a whole organ or a complete organism.

 As well as being a fascinating biological problem, regeneration has long attracted biomedical interest because of the potential of replacing or repair damaged of degenerated organs .  A range of model systems have been studied to understand regeneration. These studies have allowed the identification of multiple cellular processes that occur during regeneration. However, much less is known about the genetic mechanisms that control them. Part of the reason for this gap in our understanding is that genetic approaches for the study of regeneration in many of the classical model organisms are difficult to implement. In our lab we use as a model system an especially amenable genetic system – the developing Drosophila imaginal disc. These structures have been used as an experimental system for analysing regeneration.  Early works on disc regeneration have shown that when a fragment of the wing or leg imaginal disc is removed by microsurgery, the remaining tissue is able to regenerate the missing structures. Thus, imaginal discs are a suitable tissue to study the mechanisms that control regenerative processes . One of the goals of our project  is to exploit the new genetic tools developed in Drosophila, for analysing cellular , molecular and genetic mechanisms that underlie regeneration in imaginal wing and eye discs. In addition, Drosophila has been extensively used as a model system for genetic screenings aimed to identify new genes involved in the control of different cellular processes. We use this organism to characterize new genes involved in regeneration. As it occurs in most vertebrates in Drosophila the regenerative capacity is lost during development. One of the main goals of our research project is to learn about the fundamental genetic mechanisms involved in the decline of the regenerative ability that occurs during the development. Because the signalling pathways and their regulation are highly conserved between flies and vertebrates, there are many precedents that demonstrate the utility of using Drosophila as a model in which mechanistic details of genetic processes can be established, and then translated into other organisms. Our long-term goal is to use the insights that we obtain in Drosophila to develop testable hypotheses to identify genetic mechanisms that are required for regeneration to occur in vertebrate limbs.

Biomolecules & Cell D.
Molecular Biomedicine