@article{Coordinates:1718,
      recid = {1718},
      author = {Stedden, Claire},
      title = {Semaphorin Signaling Coordinates the Collective Migration  of Epithelial Cells in the Drosophila Egg Chamber},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2019-03},
      pages = {150},
      abstract = {Collective migration of epithelial cells is essential for  tissue morphogenesis, wound repair, and the spread of many  cancers, yet how individual cells signal to one another to  coordinate their movements is poorly understood. My  dissertation work introduces a paradigm for regulating  collective cell migration via semaphorin signaling.  Semaphorins are transmembrane guidance cues that typically  regulate the motility of neuronal growth cones and other  migrating cells by acting as repulsive cues within the  migratory environment to activate the plexin family of  receptors, which are expressed in the motile cells.  Studying the follicular epithelium of Drosophila revealed  that a transmembrane semaphorin, Semaphorin-5c (Sema-5c),  promotes collective cell migration by acting within the  migrating cells themselves, not the surrounding  environment. 

	My work focused on how Sema-5c could  promote migration in this unconventional manner. Here I  show that Sema-5c is planar polarized within the follicular  epithelium, such that it is enriched at the leading edge of  each cell. This location places it in a prime position to  send a signal to the trailing edge of the cell ahead, and  thus communicate directional information between  neighboring follicle cells during migration. My data  demonstrate that Sema-5c can signal across cell-cell  boundaries and this activity suppress protrusions in  neighboring cells. I also find that Plexin A (PlexA) is the  receptor that transduces this signal and that it is  enriched at the trailing edge of each cell, the correct  location to receive a signal from Sema-5c. PlexA interacts  with the actin disassembly factor Mical, and I present data  that are suggestive of Mical acting downstream of PlexA  during follicle cell migration. Together, these data  suggest that Sema-5c promotes collective motility by  providing a repulsive signal from the leading edge of each  cell to the trailing edge of the cell ahead.

	My work also  revealed that Sema-5c interacts with another factor that  promotes migration of the follicular epithelium, the  receptor tyrosine phosphatase Lar. Like Sema-5c and PlexA,  Lar is known for its role in nervous system development.  Overall, my studies have uncovered a system in which  multiple transmembrane guidance cues work in concert to  coordinate individual cell movements for collective  motility.},
      url = {http://knowledge.uchicago.edu/record/1718},
      doi = {https://doi.org/10.6082/uchicago.1718},
}