Characterization of behavioral phenotypes associated with changes in gene expression of components of the Irre recognition module (IRM) of Drosophila melanogaster.

• Grant number: 24/14295-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: Ricardo Guelerman Pinheiro Ramos
• Grantee: Laysa Jacome dos Santos Costalonga
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The IRM (Irre Cell Recognition Module) comprises a small, structurally related, and evolutionarily conserved group of cell adhesion molecules from the immunoglobulin superfamily, which act in a coordinated and - in some cases - partially redundant manner, across a wide range of processes during animal development. In Drosophila, mutations affecting IRM function can cause defects in ovarian morphogenesis, myoblast fusion during the development of the embryonic somatic musculature, correct patterning of the pupal retina, histolysis of the salivary gland, as well as axonal targeting of the optic lobe and the embryonic ventral nervous system where they produce behavioral phenotypes. The main goal of this project is to study the structural and functional bases of these, previously identified by our group, associated with the total or partial loss of expression of three of the IRM component genes in Drosophila melanogaster: roughest (rst), kin-of-irre (kirre), and hibris (hbs). Also in mammals, IRM components play important roles in axonal migration, synaptogenesis, and neural plasticity in brain development, and cases of moderate to severe cognitive deficiency are observed in human patients with mutations in orthologs of these gene functions. The expected results aim not only to provide a more precise understanding of IRM's operation in the Drosophila nervous system but also to contribute to a better comprehension of the general cellular and molecular mechanisms involved in mammals and the subsequent establishment of possible new therapeutic targets in humans.