Saturday, 23rd June 2018

 Development and Regeneration

        Molecular and cellular basis of Drosophila organogenesis







Sonsoles Campuzano







Research summary:

The Iroquois (iro) complex genes araucan, caupolican and mirror, encode highly related transcription factors that play a plethora of functions during organogenensis. By means of the generation of novel iro mutants, we have determined that their functions are not totally redundant. Thus, araucan and caupolican, but not mirror, define the lateral transverse muscle fate in the embryo while only mirror is involved in the specification of the dorso-ventral embryonic axis..


Model for the cis-regulation of the Iroquois Complex. The genomic DNA of the Iroquois Complex harbours enhancer sequences (red and green bars) that drive expression of reporter genes in several domains of the wing imaginal disc. These enhancers should control expression of araucan and caupolican while insulator elements (grey bar) would prevent their action on the mirror promoter.


Conversely, the three iro genes act as tumour suppressor modulating cell cycle progression at the level of the G1 to S transition. In addition, we have shown that the linkage, evolutionarily conserved, of iro genes (Irx in vertebrates) with the functionally unrelated sowah gene is due to the presence at sowah introns of enhancers that drive expression of araucan and caupolican. Action of these and other iro enhancers over mirror should be precluded by insulator sequences that we are in the process of studying (Figure 1). On the other hand, we have initiated the characterization of the iro gene regulatory network having identified two of their target genes.


Modulation of the activity of the Notch signalling pathway by DaPKC. DaPKC loss of function in the follicular epithelium prevents adequate Notch pathway activity (A, B). In the wing disc, enhanced activity of the Notch pathway was found associated to constitutive activation of DaPKC (C, D, the domain where constitutively active DaPKC is expressed is GFP labelled). Activity of the Notch pathway was monitored by expression of its target genes hnt and E(spl)m. Ooc, oocyte; wt, wild type folliclar epithelium.

Apico-basal polarity of the epithelial cells is required for development and function of numerous organs. We have recently shown how the apical determinant Crumbs contributes to trachea formation. On the other hand, loss of polarity and hyper proliferation are two hallmarks of tumour cells. Epithelial cells mutant for crumbs or the atypical protein kinase C (DaPKC) display these two traits. Thus, to investigate the causal relationship between loss of cell polarity and uncontrolled proliferation, we are studying which signalling pathways are deregulated in those mutant conditions. We have observed malfunction of the Hippo and Notch signalling pathways (Figure 2), in the latter case in association to a defective intracellular trafficking of the Notch receptor..


Latest publications:

  • Letizia, A., Sotillos, S., Campuzano, S. and Llimargas, M. (2011) Crb regulated accumulation controls apical constriction and invagination in Drosophila tracheal cells. J. Cell Sci. 124, 240- 251.
  • Carrasco-Rando, M., Tutor, A.S., Prieto-Sánchez, S., González-Perez, E., Barrios, N., Letizia, A., Martín, P., S. Campuzano and Ruiz-Gomez, M. (2011) Drosophila Araucan and Caupolican integrate in muscle precursors intrinsic and signalling inputs for the acquisition of the lateral transverse fate. PLOS Genet 7(7):e1002186.
  • Andreu, M. J., Gonzalez-Perez, E., Ajuria, L., Samper, N., Gonzalez-Crespo, S., Campuzano, S. and Jimenez, G. (2012) Mirror represses pipe expression in follicle cells to initiate DV axis formation in Drosophila. Development 139, 1110 -1114.
  • Andreu, M. J., Ajuria, L., Samper, N., González-Pérez, E., Campuzano, S., González-Crespo, S. and Jiménez, G. (2012) EGFR-dependent downregulation of Capicua and the establishment of Drosophila dorsoventral polarity. Fly 6, 234-239.
  • Maeso, I., lrimia, M., Tena, J. J, González-Pérez*, E., Trans, D., Ravi, V., Venkatesh, B., Campuzano, S., Gómez-Skarmeta J. L. and Garcia-Fernandez, J. (2012) An ancient genomic regulatory block conserved across bilaterians and its dismantling in tetrapods by retrogene replacement. Genome Res. 22, 642-655.


Doctoral Theses:

Natalia Barrios López. (2012) Las proteínas del Complejo Iroquois de Drosophila melanogaster controlan el progreso del ciclo celular y se regulan por fosforilación dependiente de MAPK. Universidad Autónoma de Madrid. Directora: Sonsoles Campuzano