Wharton Lab
Research Abstracts
Erdem Bangi:
Positional information critical for patterning of complex tissues and organs of multicellular organisms is provided by graded outputs of a number of signaling pathways (i.e BMP, Hh, Wnt). These activity gradients establish several distinct domains of target gene expression within an initially unpatterned cellular field, and these expression domains are critical for specification of multiple different cell fates. However, how such activity gradients form is not very well understood and is an intense area of investigation.
We use the A/P patterning of the Drosophila wing imaginal disc, a well characterized patterning process as a model system to study how activity gradients are established. Patterning of the wing disc along its A/P axis depends on a BMP activity gradient. In fact, a graded BMP signaling output can be visualized by an antibody that preferentially recognizes the phosphorylated version of Mad (p-Mad), the downstream effector of BMP signaling. Two BMP ligands, Gbb and Dpp, and two BMP receptors, Tkv and Sax, are implicated in wing patterning but how these BMP signaling components cooperate to form the BMP activity gradient is not understood. Currently, we are investigating the relative contributions of Gbb and Dpp along different points of the gradient. We are also studying the roles of Tkv and Sax in mediating these signals.
Figure 1. A Drosophila wing with the five longitudinal veins that form at precise locations along its A/P axis labeled L1 through L5.
Figure 2A. The BMP activity gradient established by Gbb and Dpp patterns the wing imaginal disc. A. Progenitors for the five longitudional veins (green) and the distribution of p-Mad (red) along the A/P axis of the third instar wing imaginal disc. Figure 2B. Expression patterns of Gbb (blue) and Dpp (red) in the wing disc. How these expression patterns would translate into the adult wing is also illustrated. The red line indicates the A/P boundary.
Figure 3. A third instar wing imaginal disc showing L1, L3, L4 and L5 (green) in relation to the dpp expression domain (red). Note that the dpp expression domain also represents where Gbb is required from for its long range patterning function.
Lorena D. Soares:
Specification of cell fates along the dorso-ventral axis of the Drosophila notum (dorsal thorax) is dependent on an activity gradient, visualized as graded levels of phosphorylated Mad (pMad), an intracellular transducer of BMP signaling. Our studies reveal that two BMPs, Dpp and Gbb, contribute to the establishment of this gradient, yet the contribution of each ligand to the gradient differs. While Dpp is required for patterning near its source, Gbb functions over a longer range. We are investigating the mechanism by which gbb and dpp are capable of eliciting these different responses in the presumptive notum.
Our studies investigating the relationship between two BMPs, Dpp and Gbb, revealed a previously unappreciated aspect of transcriptional regulation that is critical to ensuring the integrity of the BMP activity gradient necessary for wing and notum patterning. Our studies reveal that one of the functions of gbb in the wing imaginal disc is to downregulate dpp expression.We are currently investigating the molecular mechanism underlying this transcriptional regulation as the means by which a morphogen gradient is maintained during development is of great interest and is currently not understood.
Shannon Ballard:
The family of extracellular signaling molecules, the Bone Morphogenetic Proteins (BMPs), has been shown to regulate many developmental events in vertebrates and invertebrates, such as cell proliferation, cell fate specification, and apoptosis. In Drosophila, mutations in the BMP 5,6,7,8 ortholog, glass bottom boat (gbb), produce several defects in growth and development. In addition to patterning defects apparent in the development of imaginal tissues such as the wing and notum, gbb mutant larvae exhibit a developmental delay and demonstrate defects in the size of larval and imaginal tissues. gbb was named for the clarity of the mutant larvae, a phenotype similar to that exhibited by starved larvae.
These gbb mutant phenotypes have led to several questions of interest: What role(s) does gbb play in regulating growth? Are gbb mutants starving? Is gbb involved in the regulation of nutritional information? We have begun to investigate the relationship between the gbb mutant phenotypes and that of starved larvae as well as larvae mutant for components of pathways known to affect nutritional uptake.
