Previously, it was known that loss of Cxcr4b leads to primordium stalling. Meanwhile, Gayatri Venkiteswaran, a post-doc in our lab, made an interesting observation when she was scoring the primordium migration phenotype in chemokine receptor mutants. This gradient is available to both leader and follower cells, not just to the leader cells. These two studies demonstrated that there is a linear chemokine signaling gradient across the tissue that is essential for the directionality of the primordium. project in the Knaut lab, two studies that recently were published made my advisor Holger Knaut and me rethink the leader-follower model. When at least a few wild-type cells ended up in the front region, the migration was restored – albeit at a slower speed than the speed of wild-type primordia. They placed wild-type cells, which can see the chemokine signal into cxcr4b mutant primordia whose migration stalls prematurely. An elegant study by Haas and Gilmour generated supporting evidence for this model using chimeric analysis. It was proposed that the primordium migration also follows a leader-follower model. In terms of functionality, the model suggests that leader cells explore their surroundings extracting directional information and relaying this information to the follower cells. For example, leaders are located in front of the collective, whereas followers are located in the rear. These two groups of cells have both topological and functional attributes. In collective cell migration, a prevailing model suggests that there is a division of labor between two groups of cells: leaders and followers. Schematic of primordium migration and chemokine signaling system in primordium Importantly, the signaling receptor Cxcr4b is expressed in every primordium cell, while the Cxcr7b expression is restricted to the rear of the collective, where it acts as a sink receptor and generates a Cxcl12a gradient across the tissue. For proper migration, the primordium requires the chemokine Cxcl12a and its receptors Cxcr4b and Cxcr7b. The primordium migration is guided by chemokine signaling. The primordium is a collective of tightly adhering ~100 cells, which originates behind the ear of the fish at around 18 hours post fertilization (hpf) and migrates to the tip of the tail by 42 hpf. We used the Zebrafish lateral line primordium (primordium) as a model for our study. How do cells move as a coherent collective following guidance cues? In the latest study from our lab, my coauthors and I investigated how directional sensing in collectively migrating cells is organized. While collectively migrating cells also extract directional information and polarize toward the target site, they also have the additional task of coordinating with each other to move in the same direction and at the same speed. Single cell migration can be defined as a cell migrating on its own upon extracting directional information and polarizing and moving towards the target site. Thus, detailed studies of mechanisms of cell migration are likely to improve our understanding of animal development, homeostasis, and disease progression.Ĭell migration occurs in two major modes: single cell migration and collective cell migration. But cell migration also contributes to several pathological conditions, such as the dissemination of cancer cells to the sites of metastasis in the body. Cell migration is one of the weapons of the immune system, which sends leukocytes to the site of infection to fight against pathogens. Wounds in our bodies close by the migration of cell sheets. During development, orchestrated movements of cells pattern tissues and organs. Guided cell migration is a crucial event in many biological and mechanical processes. Jadhav, Naoya Yamaguchi, Gayatri Venkiteswaran, Heta Patel, Michael Cammer, Martin Meier-Schellersheim, Holger Knaut) Story behind our recent paper in Current Biology “Cadherin-Mediated Cell Coupling Coordinates Chemokine Sensing across Collectively Migrating Cells” (Tugba Colak-Champollion, Ling Lan, Alisha R.
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