Related Experiment Videos
Inhibition of patterned cell shape change and cell invasion by Discs large during Drosophila oogenesis
1Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA. goode@rascal.med.harvard.edu
Abstract:
Drosophila Discs large (Dlg) is a tumor suppressor gene whose loss in epithelial tissues causes disrupted cell polarity and increased cell proliferation. A human Dlg homolog, hDlg, has been implicated in tumorigenic processes via its association with the product of the Adenomatous Polyposis Coli (APC) gene. We show for the first time that Drosophila Dlg is required to block cell invasion. Loss of dlg activity during oogenesis causes follicle cells to change shape and invade in a pattern similar to border cells, a small population of cells that break from the post-mitotic follicular epithelium during wild-type oogenesis, yet dlg mutant cells have not adopted a border cell fate. Both functional and morphological evidence indicates that cooperation between germ cell and follicle cell Dlg, probably mediated by Dlg PDZ domains, is crucial for regulating cell mixing, suggesting a novel developmental mechanism and mode of action for the Dlg family of molecules. These findings suggest that Dlg does not simply inhibit individual cell behaviors during oogenesis, but rather acts in a developmental pathway essential for blocking cell proliferation and migration in a spatio-temporally defined manner. A model for Dlg action in blocking cell invasion is presented.
Insights
The Drosophila Discs large (Dlg) gene suppresses tumors by blocking cell invasion during oogenesis. Loss of Dlg causes follicle cells to invade, revealing a novel developmental role for Dlg in regulating cell proliferation and migration.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Drosophila Discs large (Dlg) is a tumor suppressor gene.
- Loss of Dlg in epithelial tissues disrupts cell polarity and increases proliferation.
- Human Dlg homolog (hDlg) is linked to tumorigenesis through APC gene association.
Purpose of the Study:
- To investigate the role of Drosophila Dlg in blocking cell invasion during oogenesis.
- To elucidate the mechanism by which Dlg regulates cell behavior and prevents abnormal migration.
Main Methods:
- Genetic analysis of dlg mutations during Drosophila oogenesis.
- Functional and morphological characterization of follicle cell behavior.
- Investigation of Dlg's interaction with germ cells and its PDZ domains.
Main Results:
- Loss of dlg activity leads to follicle cell shape changes and invasion, mimicking border cells.
- Dlg mutant cells do not adopt a border cell fate, indicating a distinct mechanism.
- Cooperation between germ cell and follicle cell Dlg, mediated by PDZ domains, is crucial for regulating cell mixing.
Conclusions:
- Drosophila Dlg is essential for blocking cell invasion during oogenesis.
- Dlg acts in a developmental pathway to prevent spatio-temporally defined cell proliferation and migration.
- A novel mechanism for Dlg family molecules in regulating cell behavior and preventing invasion is proposed.