The mysterious process that orchestrates cells to move in unison to form human and animal embryos, heal wounds, and even spread cancer depends on interaction between two well-known genetic signaling pathways, two University of Utah medical school researchers have discovered.
The study by Tatjana Piotrowski, Ph.D., assistant professor of neurobiology and anatomy, and doctoral student Andy Aman sheds new light on how the migration of groups of cells is coordinated and is the first to show a functional link between the Wnt and Fgf growth factor signaling pathways in a live animal model (zebrafish). The findings may give clues to how cancer metastasizes or spreads when cancerous cells move to different areas of the body.
Cell migration, though central to the development and maintenance of multicellular organisms, is not well understood, particularly in vivo or in live models. Researchers already knew the Wnt pathway has a role in embryogenesis and cancer by regulating cell-to-cell communication and that the Fgf pathway influences embryogenesis, wound healing, and cell proliferation. But Piotrowski's and Aman's study, published in the Nov. 11 issue of Developmental Cell , is the first to demonstrate that interaction between the two pathways is critical for proper collective cell migration.
"We looked at the question of how cells in the tip and the tail of a group of migrating cells communicate so that they move in a coordinated fashion," said Piotrowski, the paper's senior author.
To identify which genes are involved in collective cell migration, Piotrowski and Aman studied a group of migrating cells, called the lateral line primordium. During development the lateral line primordium migrates from the zebrafish head to the tail tip, periodically depositing sensory organs. The lateral line sensory system helps zebrafish and other aquatic vertebrates sense water movement.
Aman and Piotrowski discovered that both Wnt and Fgf pathway genes are activated. But for proper migration, a cellular division of labor must take place: the Wnt pathway must be restricted to the primordium's tip and the Fgf pathway must be confined to the tail. If the Wnt pathway is not restricted to cells in the tip, a cellular receptor that normally senses guidance cues is turned off and primordium cells stall and tumble randomly instead of migrating directionally, according to the researchers.
To accomplish this division of labor, each pathway stimulates the production of molecular inhibitors that restrict Wnt and Fgf pathway signaling to the tip and tail, respectively. When the Fgf pathway is activated, inhibitors are produced that restrict Wnt pathway signaling to the primordium tip. Conversely, when the Wnt pathway is activated, inhibitors are produced that restrict the Fgf pathway to the tail, the researchers reported.