Mechanisms of stress response in the Drosophila nervous system

Research summary:

Nervous system cells can be expose to a wide range of stress conditions, such as infection, hypoxia or DNA damaged by ionizing radiation (IR). Cells can response to stressful stimuli in various ways, from the activation of survival pathways, to the induction of apoptosis that eventually eliminates damaged cells. When insults result in neural damage, a regenerative response aims to preserve the structural integrity and function of the nervous system is induced. Glial cells mediate this response. Therefore, understanding the underlying mechanisms that control glial response after damage in terms of first, number and cell types, and secondly, signalling pathways that control their response, is key for developing strategies to repair the damaged tissue.

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Figure 1. Expression of Repo (green; glial cells), Elav (red; neurons) and TRE-GFP (blue, wrapping glia) in wild type control and damaged (GMR-Gal4 UAS-rpr) eye discs. Cross-sections perpendicular (top) and parallel (bottom) to the morphogenetic furrow are shown. Note how glial cells in damaged discs move to the neuron layer.

Although our knowledge about the genetic factors promoting glial regenerative response has greatly improved over the past decade, there are still many important issues about this process that remains largely unknown. To obtain a complete understanding of how these processes are regulated, it is essential to use model organisms that allow us in vivo studies, in the context of the complex interactions that take place among the different cell types that are involved. To address these issues, we take advantage of the unique developmental features of the Drosophila eye imaginal disc.

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Figure 2. Expression of Elav (green; neurons), Asense (red; neuroblasts) and Prospero (blue; GMCs) in a ganglio of third instar larva.

As we mentioned above, nerve cells can respond differently to the same stressful stimulus. Our results indicate that glial cells, and also some neuroblasts, do not die after IR. This result suggests that, either the apoptotic pathway is blocked in these cells, or the stress response induced by genotoxicity is not sufficient to activate the apoptotic pathway. Our goal is to define the genetic and molecular mechanisms that block or attenuate the apoptotic response to IR in these cells. This is relevant for understanding the mechanisms that confer high intrinsic resistance of glioma cells to irradiation.

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* For external calls please dial 34 91196 followed by the extension number
Last name Name Laboratory Ext.* e-mail Professional category
Baonza Cuenca Antonio 425 4676 abaonza(at)cbm.csic.es E.Científicos Titulares de Organismos Públicos de Investigación
Diáz-Guerro Priego Anabel 425 4608 Estudiante TFG
García Arias Juan Manuel 425 4464 Estudiante TFM
Herrero Solans Pilar 425 4464 Profesor Titular Universidad, GA
Jiménez Díaz-Benjumea Fernando 425 4676 diazbenjumea(at)cbm.csic.es E. Investigadores Científicos de Organismos Públicos

Relevant publications:

  • deHaro-Arbona, J., Baonza, A. and Díaz-Benjumea, F.J. Effects of heat shock on the cell cycle in Drosophila. Developmental Biology (under review).
  • Ahmed-de-Prado, S., Diaz-Garcia, S. Baonza, A. (2018). JNK and JAK/STAT signalling are required for inducing loss of cell fate specification during imaginal wing discs regeneration in Drosophila melanogaster.  Developmental Biology 1;441(1):31-41.
  • Ahmed-de-Prado, S. and Baonza, A. (2018). Drosophila as a model system to study cell sinalling in organ regeneration . Biomed Res Int. 2018 Mar 19;2018:7359267
  • Álvarez, J-A. and Díaz-Benjumea, F. J. (2018). Origin and specification of type-II neuroblasts in the Drosophila embryo. Development 145, dev158394 doi: 158310.151242.
  • Álvarez-Rivero, J., Moris-Sanz, M., Estacio-Gomez, A., Montoliu-Nerin, M., Diaz-Benjumea, F. J. and Herrero, P. (2017). Variability in the number of abdominal leucokinergic neurons in adult Drosophila melanogaster. J Comp Neurol 525, 639-660.
  • Díaz-García, S., Ahmed-de-Prado, S. and Baonza, A. (2016). Analysis of the function of apoptosis during the regeneration of the imaginal wing discs of Drosophila melanogaster. PLoS One. Nov 28;11:e0165554
  • Moris-Sanz, M., Estacio-Gómez, A., Álvarez-Rivero, J. and Díaz-Benjumea, F. J. (2014). Specification of neuronal subtypes by different levels of Hunchback. Development 141, 4366-4374.
  • Andrade Zapata, I. and Baonza, A. (2014). The bHLH factors Extramacrochaetae and Daughterless control cell cycle in Drosophila imaginal discs through the transcriptional regulation of the cdc25 phosphatase string. PloS Genetics. Mar 20;10(3):e1004233
  • Díaz-García, S. and Baonza, A.. (2013). Pattern reorganization occurs independently of cell division during Drosophila wing discs regeneration in situ.  Proc Natl Acad Sci USA. 110(32):13032-7
  • Estacio-Gomez, A., Moris-Sanz, M., Schafer, A. K., Perea, D., Herrero, P. and Diaz-Benjumea, F. J. (2013). Bithorax-complex genes sculpt the pattern of leucokinergic neurons in the Drosophila central nervous system. Development 140, 2139-2148.

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