Monday, 18th December 2017

 Development and Regeneration

        Signalling pathways directing wing development and                                                                                   vein pattern formation in Drosophila

 

 

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José Félix de Celis

 CSciStaff

CPublications

 

 

 

 

Research summary:

The Drosophila wing originates from an epithelial tissue (wing imaginal disc), which growth and differentiation depends on the activity of conserved signalling pathways and transcription factors. The main focus of our work is to characterise the contribution of signalling pathways to the regulation of imaginal wing disc development.

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(A) Drosophila melanogaster wild type wing (left) and domains of activation in the wing disc (red) of the Notch (Notch), Hedgehog (Hh), Epidermal growth factor receptor (EGFR), Wingless/Wnt (Wg) and Decapentaplegic/BMP (Dpp) signalling pathways. (B) Wing phenotypes resulting from manipulations in the activity of the Insulin (InR/Tor), Notch (Notch), Hedgehog (Hh) and Epidermal growth factor receptor (EGFR) signalling pathways, either by activation (column "Pathway activation") or by inhibition (column "Pathway inhibition"). (C) Wing phenotypes resulting from manipulations in the activity of the Wingless (Wg), decapentaplegic/BMP (dpp/BMP), Transforming growth factor b (TGFb) and Salvador/Warts/Hippo (SWH) signalling pathways, either by activation (column "Pathway activation") or by inhibition (column "Pathway inhibition").

Through loss- and gain-of-function genetic screens, we identified the genes gmd, MAP4K3, kurtz, kismet and spalt, and subsequently characterised their requirements during wing development.The functional analysis we carried out consisted in the generation and analysis of loss-of-function conditions, the analysis of expression patterns using in situ hybridisation, and the determination of the sub-cellular localisation of the corresponding proteins. Our studies have established the participation of these genes in the signalling pathways Notch (gmd), Insulin (Map4K3), Hedgehog (kurtz and kismet) and TGFb (spalt). We expect that the analysis in Drosophila will uncover conserved aspects of the function of these genes, which would be relevant for normal development in vertebrates and might be related with the outcome of several human genetic disorders. Our laboratory also host two Ramon y Cajal contracts, Dr. Carlos Estella y Dra. Cristina Grande. They undertake independent projects related to pattern formation in Drosophila appendages (Dr. Carlos Estella) and body plan evolution in bilateral organisms (Dra. Cristina Grande).


 

Latest publications:

  • Molnar, C., Ruiz-Gómez, A., Martín, M., Rojo, S., Mayor, F. and de Celis, J. F. (2011) Role of the Drosophila non-visual b-Arrestin Kurtz in Hedgehog signalling. PLOS Genetics 7(3): e1001335.
  • Molnar, C., Casado, M., López-Varea, A., Cruz, C. and de Celis, J.F. (2012) Genetic annotation of gain-of-function screens using interference RNA and in situ hybridization of candidate genes in the Drosophila wing. Genetics 192, 741-752.
  • Organista, M. and de Celis, J. F. (2013). The Spalt transcription factors regulate cell proliferation, survival and epithelial integrity downstream of the Decapentaplegic signalling pathway. Biology Open 15;2(1):37-48.
  • Covadonga F. Hevia and Jose F. de Celis (2013).Activation and function of TGFβ signalling during Drosophila wing development and its interactions with the BMP pathway. Dev. Biol. 377: 138-153.
  • Jose F. de Celis (2013). Understanding the determinants of Notch interactions with its ligands. Sci Signal. 6, pe.19.

 

Doctoral Theses:

Martín Resnik Docampo (2011). La proteína MAP4K3 participa, a través de mecanismos independientes, en la regulación de las rutas de señalización Tor y JNK. Universidad Autónoma de Madrid. Director Jose F. de Celis.

María Fernández Organista (2012). Funciones de las proteínas Spalt e identificación de sus genes diana durante el desarrollo del disco imaginal de ala de Drosophila melanogaster. Universidad Autónoma de Madrid. Director Jose F. de Celis.