Primordial Germ Cell Migration
Boldajipour B, Mahabaleshwar H, Kardash E, Reichman-Fried M, Blaser H, Minina S, Wilson D, Xu Q, Raz E. 2008. Control of chemokine-guided cell migration by ligand sequestration.
Cell. -Blaser H, Reichman-Fried M, Castanon I, Dumstrei K, Marlow FL, Kawakami K, Solnica-Krezel L, Heisenberg CP, Raz E. 2006. Migration of zebrafish primordial germ cells: a role for myosin contraction and cytoplasmic flow. Dev Cell. 11(5):613-27.
Briefly tell us a bit about yourself, your career path over the years, and specifically what led you to begin working on primordial germ cell migration in zebrafish.
What is the relationship between the “run” and “tumbling” phases in PGC migration? I understand that migrating PGCs alternate between these two phases, but why are both necessary for the PGCs to migrate to their target site? What is the mechanism that controls alternating between the two phases?
Why did you analyze only 5-8 cells during the tumbling phase, while you analyzed 25-33 cells for migration speed? Do you think this large difference in the number of cells analyzed for migration speed, run speed and tumbling would affect your results?
In the paper “Migration of Zebrafish Primordial Germ Cells: A Role for Myosin Concentration and Cytoplasmic Flow” there is a discussion about Dictyostelium and how it has similar migration characteristics to those observed in zebrafish. I am confused about this comparison. Can you please elaborate on what characteristics are similar between the two systems, and then comment on how applicable your models of PGC migration is to the mammalian system?
What cells are responsible for secreting SDF1? What prompts them to secrete SDF, and what regulates when and how much of the chemoattractant is released?
Are SDF-1a gradients fully established prior to the beginning of PGC migration? Or is the process more dynamic—in other words, is CXCR7 actively clearing away SDF-1a as a result of PGCs reaching sdf-1a transcription domains? If the latter is the case, have you identified any mechanisms by which CXCR7 activity can be regulated in response to incorrect migration patterns?
PGCs migrate to intermediate locations before moving on to their ultimate destination, and you’ve shown that SDF-1 is the attractant molecule that interacts with the receptor CXCR4 to help guide PGC’s and CXCR7 is necessary in the migratory pathway, possibly to sharpen SDF-1 gradient. Is there communication between the various intermediate destinations and target site? Does the final destination act first, secreting a factor activating the intermediate locations to secrete SDF-1? Do the PGCs themselves secrete a factor to activate it’s own homing beacon?
What other guidance cues exist that migrating PGCs use besides SDF-1 and how do they work? Are they attractants, repellants, and how do PGC detect subtle differences in such environmental cues?
Why do you think evolution would favor having intermediate (and possibly out-of-the-way) targets for PGCs to migrate toward (as seen in your experiments and such as the allantois in mammals) rather than just having the PGCs move more directly to their final positions in the gonads or even more simply by being born in the presumptive gonad regions?
Currently in your opinion what are the most pressing questions in the field of primordial germ cell migration, and what steps is your lab taking to address those questions?