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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01GM068675-10A1
Application #
8824805
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Hoodbhoy, Tanya
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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