Biomedical subjects

Jocelyn A McDonald

Publications and source records attributed to Jocelyn A McDonald.

4 recordsLinked to original sources

PubMed2006

Multiple EGFR ligands participate in guiding migrating border cells.

Cell migration is an important feature of embryonic development as well as tumor metastasis. Border cells in the Drosophila ovary have emerged as a useful in vivo model for uncovering the molecular mechanisms that control many aspects of cell migration including guidance. It was previously shown that two receptor tyrosine kinases, epidermal growth factor receptor (EGFR) and PDGF- and VEGF-related receptor (PVR), together contribute to border cell migration. Whereas the ligand for PVR, PVF1, is known to guide border cells, it is unclear which of the four activating EGFR ligands function in this process. We developed an assay to detect the ability of secreted factors to reroute migrating border cells in vivo and tested the activity of EGFR ligands compared to PVF1. Two ligands, Keren and Spitz, guided border cells whereas the other ligands, Gurken and Vein, did not. In addition, only Keren and Spitz were expressed at the appropriate stage in the oocyte, the target of border cell migration. Therefore, a complex combination of EGFR and PVR ligands together guide border cells to the oocyte.

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PubMed2005

Analysis of cell migration using Drosophila as a model system.

There are a number of reasons to use Drosophila as a model system to study cell migration. First and foremost is the availability of an arsenal of powerful genetic techniques that can be deployed, permitting the study of cell migration in vivo, in the context of the entire organism. This is especially important for the study of a complex behavior that can be dramatically affected by small changes in environmental conditions. Several different types of cell migrations occur during Drosophila development. In this chapter, we focus on cell migrations that have been subjected to the most intense scrutiny. We describe each of the cell types and their trajectories and provide information regarding markers that are useful for the study of each cell type and mutations that affect their migrations. In addition, we provide protocols for staining embryos and manipulating gene function in each of the migratory populations. Finally, we offer some advice concerning the analysis and interpretation of mutant phenotypes.

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PubMed2003

Specification of motoneuron fate in Drosophila: integration of positive and negative transcription factor inputs by a minimal eve enhancer.

We are interested in the mechanisms that generate neuronal diversity within the Drosophila central nervous system (CNS), and in particular in the development of a single identified motoneuron called RP2. Expression of the homeodomain transcription factor Even-skipped (Eve) is required for RP2 to establish proper connectivity with its muscle target. Here we investigate the mechanisms by which eve is specifically expressed within the RP2 motoneuron lineage. Within the NB4-2 lineage, expression of eve first occurs in the precursor of RP2, called GMC4-2a. We identify a small 500 base pair eve enhancer that mediates eve expression in GMC4-2a. We show that four different transcription factors (Prospero, Huckebein, Fushi tarazu, and Pdm1) are all expressed in GMC4-2a, and are required to activate eve via this minimal enhancer, and that one transcription factor (Klumpfuss) represses eve expression via this element. All four positively acting transcription factors act independently, regulating eve but not each other. Thus, the eve enhancer integrates multiple positive and negative transcription factor inputs to restrict eve expression to a single precursor cell (GMC4-2a) and its RP2 motoneuron progeny.

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PubMed2003

PVF1, a PDGF/VEGF homolog, is sufficient to guide border cells and interacts genetically with Taiman.

The border cells of the Drosophila ovary undergo a well-defined and developmentally regulated cell migration. Two signals have previously been shown to control where and when the cells migrate. The steroid hormone ecdysone, acting through its receptor and a coactivator known as Taiman, contributes to regulating the timing of border cell migration. PVF1, a growth factor related to platelet-derived growth factor and vascular-endothelial growth factor, contributes to guiding the border cells to the oocyte. To probe the mechanisms controlling border cell migration further, we performed a screen for genes that exhibit dominant genetic interactions with taiman. We identified 14 genomic regions that interact with taiman. Within one region, we identified Pvf1 as the gene responsible for the interaction. Signaling by PVF1 has been proposed to guide the border cells to their proper target, but ectopic PVF1 has not been tested for its ability to redirect the border cells. We tested the ability of PVF1, as well as other factors such as Gurken, to guide the border cells to new targets. Our results demonstrate that ectopic expression of PVF1 is sufficient to redirect border cells in some egg chambers but that the other factors tested are not. These data suggest that the guidance of border cell migration is robust and that there are likely to be additional factors that contribute to long-range guidance of these cells. In addition, we find that taiman and Pvf1 regulate the dynamic localization of E-cadherin in the border cells, possibly accounting for the interaction between these two pathways.

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