The cellular mechanisms that drive morphogenesis are a key frontier of Developmental Biology. Beyond their basic fascination, elucidating these mechanisms is a major obstacle to biomedical goals ranging from understanding congenital defects in organogenesis to engineered organ culture. Despite a detailed understanding of several paradigmatic examples, we currently understand how only a fraction of the astonishing diversity of organs take shape. To expand knowledge of the morphogenetic repertoire, we study how the Drosophila follicle, a structurally and geometrically simple organ, undergoes a tissue elongation to produce a distinctive oval egg. Using live imaging, we have discovered an unexpected morphogenetic behavior in which the entire organ executes several complete, planar-polarized rotations around its circumferential axis. Strong evidence indicates that this collective cell migration drives organ elongation. Intriguingly, recent data from topologically analogous vertebrate systems raise the possibility that planar-polarized rotation may be conserved. The new morphogenetic movement represented by follicle rotation, in which PCP collective cell migration of an 'edgeless'tissue drives its elongation, shares important elements with familiar morphogenetic paradigms in 'edged'organs. It also presents a number of distinctive features that must involve new biology. We will exploit this exciting discovery to uncover mechanisms underlying this alternative strategy of tissue extension. To do so, we will address the following questions: 1). How is PCP organized in the follicle, which is independent of conventional PCP regulators? 2). How does collective migration around a tissue axis lead to elongation along that axis? 3). What molecular mechanisms control PCP rotation and tissue elongation? The answers to these questions will reveal new principles and mechanisms that drive morphogenesis, and move us towards a more complete understanding of how organs are shaped.
Elongation of many human tissues requires execution of cell movements that are polarized within the plane of the tissue. While those in 'edged'tissues are relatively well-understood, the cellular and molecular mechanisms underlying many, including 'edgeless'tubules, remain unknown. We have discovered a new type of collective cell movement that elongates an 'edgeless'tissue in the fruit fly and occurs independently of familiar morphogenetic pathways;this proposal will uncover the underlying mechanisms, forming a basis for understanding analogous processes that may shape human organs as well.
|Skwarek, Lara C; Windler, Sarah L; de Vreede, Geert et al. (2014) The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells. Development 141:2978-83|
|O'Brien, Lucy Erin; Bilder, David (2013) Beyond the niche: tissue-level coordination of stem cell dynamics. Annu Rev Cell Dev Biol 29:107-36|
|Buster, Daniel W; Daniel, Scott G; Nguyen, Huy Q et al. (2013) SCFSlimb ubiquitin ligase suppresses condensin II-mediated nuclear reorganization by degrading Cap-H2. J Cell Biol 201:49-63|
|Haigo, Saori L; Bilder, David (2011) Global tissue revolutions in a morphogenetic movement controlling elongation. Science 331:1071-4|
|Banks, Susan M L; Cho, Bomsoo; Eun, Suk Ho et al. (2011) The functions of auxilin and Rab11 in Drosophila suggest that the fundamental role of ligand endocytosis in notch signaling cells is not recycling. PLoS One 6:e18259|
|O'Brien, Lucy Erin; Soliman, Sarah S; Li, Xinghua et al. (2011) Altered modes of stem cell division drive adaptive intestinal growth. Cell 147:603-14|
|Vaccari, Thomas; Duchi, Serena; Cortese, Katia et al. (2010) The vacuolar ATPase is required for physiological as well as pathological activation of the Notch receptor. Development 137:1825-32|
|Windler, Sarah L; Bilder, David (2010) Endocytic internalization routes required for delta/notch signaling. Curr Biol 20:538-43|
|Classen, Anne-Kathrin; Bunker, Brandon D; Harvey, Kieran F et al. (2009) A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. Nat Genet 41:1150-5|
|Vaccari, Thomas; Bilder, David (2009) At the crossroads of polarity, proliferation and apoptosis: the use of Drosophila to unravel the multifaceted role of endocytosis in tumor suppression. Mol Oncol 3:354-65|
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