608A Poster - 08. Patterning, morphogenesis and organogenesis
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
mo weng ¹; Rolin Sauceda ^{1, 2}

Affiliations:
1) University of Nevada, Las Vegas; 2) Stanford University School of Medicine

Keywords:
q. epithelial sheets; b. cell polarity

Epithelial-to-mesenchymal transition(EMT) converts cells from highly connected and apicobasally polarized epithelial states into detached and often migratory mesenchymal states. It is an essential process during development and its misregulation underlies tumorigenesis. In the conventional model, a key step in EMT is to eliminate cell-cell junctions through transcriptional repression by EMT transcription factors, such as the conserved EMT driver Snail. However, recent advances suggest most EMTs display reversible intermediate states and do not reach the final mesenchymal state where junctions are completely lost. We show previously that in Drosophila gastrula, Snail drives EMT in mesoderm through a post-transcriptional mechanism: disassembling junctions through downregulation of polarity protein Bazooka/Par-3. Here we show that this downregulation of Bazooka/Par-3 is through a cytoplasmic sequestering of Bazooka/Par-3 proteins. Snail is necessary and sufficient in downregulating cortical Bazooka/Par-3. Despite the loss of cortically localized Bazooka/Par-3, we do not observe significant changes in Bazooka/Par-3 protein levels upon Snail overexpression in embryo extracts. To examine the change in cytoplasmic levels of Bazooka/Par-3 in response to Snail expression, we induced Snail overexpression clones in egg chamber follicle epithelium which normally do not express Snail. We find that the Snail-dependent downregulation of cortical Bazooka/Par-3 is accompanied by an increase in cytoplasmic levels of Bazooka/Par-3 proteins. This suggests Baz is regulated at post-translational levels and preferentially localizes in cytoplasm. In addition to the loss of Bazooka/Par-3 and adherens junctions, Snail expression in these cells also leads to cell flattening and even delamination from the follicle epithelium. Overall, these results suggest a post-translational pathway is downstream of Snail in regulating Bazooka/Par-3 localization and it provides a possible molecular mechanism for EMT intermediate states.