The Developmental Molecular Genetics and Biomedical Models group works on two main research lines:

1 . Use of Drosophila as a model for studying human genetic diseases

Our group is particularly interested in the study of Parkinson’s disease (PD), the second most common neurodegenerative disorder. While most PD cases are sporadic, familial forms account for 5–10% and are caused by mutations in specific genes. Oxidative stress (OS) is a key factor in PD pathogenesis, mainly due to mitochondrial dysfunction. Among the genes implicated, DJ-1 is most closely linked to oxidative stress. Mutations in this gene cause an autosomal recessive early-onset form of PD. DJ-1 performs several critical functions in oxidative stress response, acting as a ubiquitous, cytoprotective redox sensor and regulating gene expression related to oxidative stress defense. 

In our lab, we have developed a Drosophila PD model using mutants in the DJ-1β gene (the fly homolog of human DJ-1). These mutants exhibit high levels of oxidative damage and reproduce PD-related phenotypes such as increased sensitivity to oxidative stress and motor defects. In this model, we aim to identify proteins specifically modified by oxidation that may be relevant in PD pathogenesis. The goal is to identify a set of genes with human homologs involved in PD, which could become biomarkers or therapeutic targets.

Since PD is currently incurable and only symptomatic treatments are available, we are also searching for compounds that can suppress motor defects and reduce oxidative stress levels in the fly model. These candidate compounds will later be validated in vertebrate models and may serve as potential therapeutics for this disease.

2 . Study of Basic Developmental Processes in Drosophila Relevant to Human Health

Our group is also interested in studying basic developmental processes in Drosophila such as embryonic dorsal closure, wound healing, and the establishment of planar cell polarity, which are relevant to human health. This is a basic research line with an applied projection, and its specific objectives are:

a . Study of Embryonic Dorsal Closure and Wound Healing in Drosophila
Dorsal closure (DC) is a morphogenetic process that occurs toward the end of Drosophila embryonic development. This process involves migration and fusion of epithelial layers and is used as an in vivo model for wound healing in vertebrates. Understanding the molecular bases of wound healing and regeneration is one of the main challenges in biology and medicine, leading to medical advances that could accelerate the healing of damaged tissues, the reconstruction of tissues/organs, and the restoration of homeostasis. Drosophila is a good model for this study because both the cellular machinery and the signaling pathways involved in embryonic DC and wound healing in this organism are similar to those in vertebrates. The aim of this research line is to identify new regulatory mechanisms involved in embryonic DC and wound healing in Drosophila and to analyze cell dynamics by combining genetic techniques with advanced live-imaging and high-throughput sequencing methods. In this context, we are determining the function and transcriptional targets of Cabut (Cbt), a transcription factor involved in DC and regeneration in Drosophila. Since Cbt is the Drosophila ortholog of vertebrate TIEG proteins, which play a role in wound healing, some of our results could be transferable to humans and serve as a starting point for future research on this process.

b . Study of the Establishment of Epithelial Planar Cell Polarity in DrosophilaIn multicellular organisms, epithelia are polarized not only along the apico-basal axis but also within the plane of the epithelium, known as epithelial planar cell polarity (PCP). In Drosophila, PCP is manifested in various body structures such as the adult eye, where cells of each ommatidium are precisely organized relative to each other and to the dorsoventral and anteroposterior axes. This pattern is generated in the eye imaginal disc and involves two distinct but related steps: the establishment of asymmetry (chirality) in forming ommatidia, associated with the specification of the R3/R4 photoreceptor pair, and a subsequent 90º rotation of the ommatidia toward the equator. PCP establishment in Drosophila is partly regulated by the Egfr pathway and by an atypical Wnt pathway, the Fz/PCP pathway, which is evolutionarily conserved and controls processes in vertebrates such as convergent extension—responsible for elongation of the body axis—and other processes involving collective cell movements like metastasis. The aim of this research line is to identify new genes involved in this process and study how it occurs at the cellular level. One of the recently identified genes encodes the ortholog of vertebrate MK and PTN proteins, which are secreted cytokines involved in cell migration and cancer, functioning by activating signaling pathways.