Thursday, 14th December 2017

Development and Regeneration

         Genetic control of morphogenesis

 


Grupo-400

 


Ginés Morata Pérez

CSciStaff

CPublications

 

Research summary:

In recent years the research of our group has focussed on two major research lines: 1) the study of cell competition, especially in relation with apoptosis and tumorigenesis, and 2) experimental analysis of regeneration in the imaginal discs.

Regarding cell competition, we have shown that it functions as a tumour suppressor mechanism, inducing apoptosis in oncogenic cells. We are presently analysing the mechanisms by which tumour cells may evade the control by cell competition and proceed to develop a tumour. Recent results (Ballesteros-Arias et al 2014) indicate that they can evade cell competition by forming a protective microenvironment of about 500-600 cells. In this situation, cell competition induces apoptosis in the cells at the periphery of the tumour, but it being a short-range phenomenon, tumour cells in the centre of the group are beyond its range and continue proliferating. Under these circumstances cell competition reverses its normal anti-tumour role and functions as a tumour stimulating factor, due to the proliferative signals that emanate from the tumour cells in apoptosis at the border of the tumour. We are presently trying to identify the factors involved in the tumorigenesis by apoptotic cells. The connection between apoptosis and tumour growth may have relevant clinical implications.

The second research line has been the analysis of regeneration in the imaginal discs; the overall aim is the study of the genetic reprogramming mechanisms during the reconstruction of structures that have been damaged or eliminated. Our recent publications (Herrera et al 2013; Herrera and Morata, 2014, see also review in Morata and Herrera 2016) have demonstrated that during regeneration the epigenetic control of cell identities breaks down transiently, allowing for changes in the identity of the affected cells, which reconstruct the missing organ. These cells become reprogrammed by a novel mechanism that requires interactions with their neighbours.

In forthcoming years we plan to carry out a comprehensible study of regeneration of the different body parts of Drosophila using new tracking methods to follow the regeneration processes. We will be paying special attention to the regenerative response of different regions within the imaginal discs, in particular the distinction between body trunk and appendages, an issue that has been hitherto neglected.

fig1

Drosophila wing disc containing a marked clone (green) deficient for the pro-apoptotic genes and over-expressing the JNK pathway. The cells of the clone express the metalloprotease 1, which degrades extracellular matrix. Note the presence of F-actin protrusions (blue) at the basal region of the cells

fig2

Wing imaginal disc in which posterior compartment cells (right side) have suffered a treatment of 2 days of apoptosis induction followed by 3 days of recovery. The cells belonging to the posterior lineage are labeled in yellow, while the anterior compartment is labeled in magenta. Note the presence of groups of cells (asterisks) that were originated in the posterior compartment and now belong to the anterior compartment. This result suggests that the ablation treatment provokes a transient collapse of the compartments boundary and a change in cell identity

 

 

Latest publications:

  • Herrera, S. Martin, R. and Morata. G. (2013) "Tissue homeostasis in the wing disc of Drosophila: immediate response to massive damage during development" PLoS Genet 9 (4), e10034446
  • Morata, G and Herrera, S. (2013) "Eiger triggers death from afar" eLife 2:e01388. doi: 10.7554/eLife.01388
  • Herrera, S and Morata, G. (2014) "Transgressions of compartment boundaries and cell reprogramming during regeneration of the imaginal discs of Drosophila" eLife. 3: e01831. doi: 10.7554/eLife.01831
  • Ballesteros-Arias, L., Saavedra V, and Morata, G. (2014) "Cell competition may function either as tumour-suppressing or as tumour‐stimulating factor in Drosophila". Oncogene 33, 4377-4384
  • Morata, G. and Struhl, G. (2014) "Tethered wings" Nature 505, 162-163
  • Morata, G. and Ballesteros-Arias L. (2014) "Death to the losers. Cell competition is linked to innate immunity mechanisms to eliminate unwanted cells and maintain healthy tissue". Science 346, 1181-1182
  • Morata, G. and Ballesteros-Arias, L. (2015) "Cell competition, apoptosis and tumour development" Int. J. Dev. Biol. 59, 79-86
  • Morata G. and Herrera, S.C. (2016) "Cell reprogramming during regeneration in Drosophila: transgression of compartment boundaries" Current Opinion in Genetics & Development 40, 11-16
  • Calleja, M. Morata, G and Casanova, J. (2016) "The tumorigenic properties of Drosophila epithelial cells mutant for lethal giant larvae". Dev. Dynamics in press

 


 

Doctoral theses:

  • Evgeny Shlevklov (2011) Nuevos mecanismos de regulación de la apoptotis en Drosophila melanogaster. Universidad Autónoma de Madrid. Director: Ginés Morata Pérez.
  • Javier Ménendez González (2011) Competición celular y desarrollo de tumores en discos imaginales de Drosophila. Universidad Autónoma de Madrid. Director: Ginés Morata Pérez.