Dr. Ann Sutherland

Gastrulation in the Mouse

Yen WW, Williams M, Periasamy A, Conaway M, Burdsal C, Keller R, Lu X, Sutherland A. 2009. PTK7 is essential for polarized cell motility and convergent extension during mouse gastrulation. Development 136(12):2039-48.

Nowotschin and Hadjantonakis 2010. Cellular dynamics in the early mouse embryo: from axis formation to gastrulation. Current Opinion in Genetics and Development 20:420-427.

Behringer et al. 2000. A flattened mouse embryo: leveling the playing field. Genesis 28:23-30.

Question 1

Briefly tell us a bit about yourself, your career path over the years, and specifically what led you to begin working on gastrulation in the mouse. Additionally, as you are an expert on mouse gastrulation, could you briefly summarize the somewhat overlapping but sequential steps of gastrulation in the mouse to provide a framework for today’s discussion.

Michael J. F. Barresi

Question 2

What background knowledge led you to suspect PTK7 as a regulator in mediolateral cell intercalation?

Mary Roh

Question 3

In the article it states that “PTK7 is a pseudokinase and thus unlikely to be signaling directly by phosphorylation.” Is it known how PTK7 signals exactly?

Charmaine Rivera

Question 4

Protrusive behavior is said to be controlled by PTK7, however why is it only after the primitive streak that PTK7 mutants and WT are distinguishable? Why is the polarization of cells during the primitive streak not affected by loss of PTK7?

Sarah Izen

Question 5

In the mouse, both epithelial and mesenchymal tissues undergo convergent extension – are there any differences in the cell behaviors or molecular players between the two tissues when undergoing CE?

Yvanka De Soysa

Question 6

In the article, it states that “Vangl2 and Ptk7 do interact genetically, as compound heterozygotes exhibit a more severe phenotype that either single heterozygote (Lu et al., 2004). However, the phenotype of the compound heterozygote is also unlike that of either single homozygote, suggesting that the two genes may act in separate pathways that both affect axial extension and neural tube closure.” I was wondering. In what ways are the phenotypes of the compound heterozygote different from either single homozygote and thus supporting separate pathways? Also, have you looked into the possibility of other separate pathways that affect axial extension and neural tube closure? If so, what are these possible pathways?

Samantha Torquato

Question 7

You noticed that, in the Ptk7 mutant, DVL localization was not changed. If DVL is not affected in the mutant, how do you hypothesize that Ptk7 regulates cell movement, if it doesn’t affect “gross aspects of DVL2 distribution or of cytoskeletal organization.”

Rachael Stein

Question 8

You mentioned that forces produced by radial intercalation oppose the tendency for convergence forces to thicken and elongate the tissue, and that in the mutant embryos there was concomitant, unopposed radial intercalation that broadened the somitic mesoderm field. What is driving the concomitant radial intercalation?

Zarnab Iftikhar

Question 9

The mouse somitic mesoderm has a “zigzag” movement phase, accompanied by multipolar protrusive activity. It seems to me that at this phase, the cells constantly reevaluate the environment (their relative position in the embryo) and adjust their track accordingly by changing the protrusive activity. Then in the later phase, the cells are bipolar and show no zigzag pattern (The cells seem to be more certain). What causes this change? Would there be a Ptk7 signaling gradient pattern involved?

Yisi Lu

Question 10

Getting a little away from gastrulation, I read that Ptk7 is expressed in colon carcinoma tumors but not in normal colons. Does this mean that Ptk7 is involved in tumor development? What are some of the clinical implications for Ptk7 or any other genes involved in gastrulation?

Carla Velez

Question 11

Currently in your opinion what are the most pressing questions in the study of Mouse gastrulation, and what steps is your lab taking to address these questions?

Michael J.F. Barresi