Gene Dog Blog

A recent Mol Cell Biol paper highlights the in vivo function of the Drosophila homolog of human Nm23, abnormal wing discs (awd), in regulating the epithelial integrity during Drosophila oogenesis.

Pubmed abstract:

Mol Cell Biol. 2009 Jul 6. [Epub ahead of print]Click here to read

The Drosophila metastasis suppressor Nm23 homolog, awd, regulates epithelial integrity during oogenesis.
Woolworth JA, Nallamothu G, Hsu T.

Department of Pathology and Laboratory Medicine, and Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425.

The expression levels of the metastasis suppressor gene Nm23 have been shown to correlate positively or inversely with prognosis in different cancer cohorts. This indicates that Nm23 may be needed at different expression levels and may function differently in various tissues. Here we report a novel epithelial function of the Drosophila homolog of human Nm23, abnormal wing discs (awd). We show dynamic expression pattern of Awd protein during morphogenesis of the Drosophila follicle cells during oogenesis. Loss-of-function awd mutant cells result in accumulation and spreading of adherens junction components such as DE-cadherin, beta-catenin/Armadillo and alpha-spectrin, and disruption of epithelial integrity including break up of epithelial sheet and piling up of follicle cells. By contrast, over-expression of awd diminishes adherens junction components and induces mesenchymal-like cell shape change. The gain-of-function phenotype is consistent with a potential oncogenic function of this metastasis suppressor gene. Interestingly, we demonstrate that the epithelial function of awd is mediated by Rab5 and show that Rab5 expression level is down-regulated in awd mutant cells. Therefore, awd modulates the level and localization of adherens junction components via endocytosis. This is the first demonstration of an in vivo function of Nm23 family genes in regulating epithelial morphogenesis.

Interestingly, the authors also demonstrate that Rab5 expression level is down-regulated in awd mutant cells, indicating a deffect of endocytosis in the disruption of the epithelia integrity. However, the exact role of endocytosis in the control of epithelial morphogenesis seems to need further investigation.

Incoming search terms:

• Drosophila metastasis suppressor and regulates epithelial morphogenesis via endocytosis
• metastasis drosophila