Dr. Carol Erickson and Dr. Melissa Harris

Neural Crest Migration

Harris, M. L., Hall, R. and Erickson, C. A. (2008). Directing pathfinding along the dorsolateral path- the role of EDNRB2 and EphB2 in overcoming inhibition. Development 135, 4113-4122.

Harris, M. L. and Erickson, C. A. (2007). Lineage specification in neural crest cell pathfinding. Dev. Dyn. 236, 1-19.

Question 1

Briefly tell us a bit about yourselves, your career paths over the years, and specifically what led you to begin working on Neural Crest migration in the Chick.

Michael Barresi

Question 2

I understand that pre-specified melanoblasts have specific receptors which are upregulated in your model, but by what mechanism does EDNRB2 begin to be upregulated to trigger the advance of melanoblasts from the MSA to the DL pathway?

Helene Parker

Question 3

I understand that both EBNRB2 and EphB2 receptors are necessary for dorsolateral migration of melanoblasts and that EBNRB2 can rescue the loss of EphB2. Why are both of the receptors necessary? Are both needed in equal amounts or is one upregulated/downregulated more than the other at different times?

Carolyn Cunha

Question 4

Are EphB2 and EDNRB2 responsive to the same inhibitors? Is it possible that EphB2 overexpression inconsistently compensates for EDNRB2 knockdown due to a differential interaction with inhibitors?

Sarah Wardlaw

Question 5

I understand that EphB2 is the specific receptor that mediates the attachment to fibronectin, but you mention that there may be more signaling systems involved in the transition between migratory pathways, like chemoattractants. Could you talk more about these other possible signaling systems, specifically the role ephrin Bs and ET3 play in your proposed model for melanoblast DL migration?

Jillian Merica

Question 6

In the paper you hypothesized that the loss of repulsive molecules in the environment (repellants such as chondroitin-6-sulfate, PNA-binding molecules and F-spondin) may allow the DL to become “permissive” enough for melanoblasts to use this domain. Do you know yet of any substance or cell that is inhibiting these inhibitors at the time of melanoblast migration (or even a cell that acts as a sink for these molecules)?

Kimberly Johnson

Question 7

Do you think that there are cells in the pathway expressing receptors that help to sharpen the gradients as there are in primordial germ cell migration pathways, similar to what is observed in the interactions between CXCR7 and SDF1 during PGC migration in zebrafish?

Hanna Sherrill

Question 8

Some neural crest cells are pre-specified and some are not. Why do you suppose this is? What might the advantage be if any for a NCC to be pre-determined? Is there a specific advantage to its ability to choose an appropriate pathway?

Rebecca Jacobson

Question 9

You say in your conclusion that you are interested in applying your findings in other model systems. Have you begun to look at applications in other model systems, maybe even in humans, medically or otherwise? How have you or are you planning to reconcile the deviations you see in chick melanoblast migration with those of mice, such as the varying role of c-Kit between the two organisms?

Sarah Bashiruddin

Question 10

Currently in your opinion what are the most pressing questions in the field of neural crest cell migration, and what steps is your lab taking to address those questions?

Michael Barresi