During metazoan development, a small number of signaling pathways are iteratively used to orchestrate diverse processes such as cell fate determination, apoptosis, cell proliferation, and cell migration. The coordinated temporal and spatial regulation of these pathways underlies the final cellular makeup, size, and shape of organs and dysregulation of these pathways can lead to human diseases.
We take advantage of the powerful genetic and molecular techniques (including genome engineering) available in Drosophila, which facilitate both gene discovery and in vivo analysis of gene function, to study developmental, cellular and molecular mechanisms involved in organ formation.
Our studies focus on the BMP, WNT, Notch, EGFR and Hedgehog signaling pathways. We are particularly interested in the comparative analysis of the responses to these signaling pathways in various developmental and experimental contexts wherein their transcriptional outputs are collaborative, mutually exclusive or even antagonistic.
Elucidation of such outcomes, especially the unusual ones, has allowed us to identify new strategies, feedback loops and "twists" in the transcriptional cascades underlying the ‘logic’ of the developmental programs.
Developmental genes operating in the developing wing disc.
Wingless (blue), Scalloped(green), Splat(red)
A second niche of our work is that we are using Drosophila as a model system to understand aberrations that are at the heart of human diseases.
For example, we study (in collaboration with endocrinologists and human geneticists) a cohort of consanguineous families with familial XX-Ovarian Dysgenesis, each with multiple affected females. Using homozygosity mapping and whole exome sequencing, combined with bioinformatics, we attempt to identify mutation-causing candidate genes. Where homologous Drosophila genes exist, we generate a comparable fly model, using it to elucidate the functions and pathways in which they are involved. We have already identified Nucleoprin107 as a key player in ovarian development and dysgenesis. This fly model offers a powerful platform to identify soma-germline signaling and new genes operating in ovarian development.
Germ and somatic cells in the gonad of female larvae. Somatic cells and fusomes within germ cells outlined by Hts-1B1 staining (green). Germ cells stained with Vasa (blue)
Nucloporin (Nup) 107 expression in the ovary of adult fly. GFP-Nup107 in green. Actin in red.