1) Genetic and epigenetic control of imaginal discs regeneration

One of the most fascinating challenges to Developmental Biology in the so-called post-genomic era is to understand the mechanisms that control regeneration. In order to meet that challenge, fundamental questions must be answered, such as how the size of lost structures is recovered, how proliferation is controlled, and how cells retain a “memory” that allows genetic programs established during early development to be maintained. Genes of the polycomb (PcG) and trithorax (trxG) families, which control gene expression by modifying chromatin structure, form the basis of cell memory. The main aim of this project is to address the contribution of genes of the trithorax group to cell memory during normal development of the Drosophila imaginal discs and following experimental induction of regeneration. An understanding of the molecular details that underlie epigenetic mechanisms could be crucial for the comprehension of the maintenance of developmental decisions in regenerating tissues. Some of these questions are addressed using genetic and cellular experimental approaches. We also are using DNA microarray technology and genetic designs to decipher the molecular and cellular basis of imaginal disc regeneration.

2) Cell signaling: differentiation of the photoreceptor R7

An important challenge for developmental biologists is to unravel the complex gene regulatory networks through which signaling pathways interact to promote growth and development. A simple model with which to approach the relationship between genetic interactions and cell-fate determination is the interaction between the R8 and R7 photoreceptor. This is addressed in our laboratory by identifying and characterizing negative regulators of signaling through the receptor tyrosine kinase sevenless.

The development of photoreceptor cells is controlled by a variety of cell signaling mechanisms. Among them, the activation of the Sevenless receptor tyrosine kinase plays a pivotal role in the determination of the photoreceptor R7. Although that pathway is well characterized, negative regulators and their link to other pathways are not well understood. We have used a genetic screening design to search for genes that modify phenotypes caused by the overexpression of the sevenless RTK. We are currently analyzing those genes and dissecting their role in photoreceptor development.

Cells have developed a complex network of mechanisms to preserve the redox balance and to scavenge reactive oxygen species (ROS) generated as metabolic byproducts. The family of selenoproteins drives one of those mechanisms. Selenoproteins have an antioxidant function and are characterized by containing the aminoacid selenocysteine. An evolutionary conserved machinery controls the incorporation of selenocysteine into the selenoprotein polypeptide chain. One of the elements of that machinery is the selenophosphate synthetase. In eukaryotes, two variants of this enzyme have been found: the Sps2, which is a selenoprotein itself, and the SelD/sps1. We have identified a mutation of the Drosophila SelD/sps1 gene that perturbs the biosynthesis of selenoproteins and demonstrated its function in cell proliferation, signaling transduction and apoptosis. Our work focuses on whether the selD/sps1 protein shares a common function with sps2 or alternatively it has derived to a novel function. We have also identified the selenoproteins in Drosophila and we are currently studying their function in growth and differentiation.