Dr. Marianne Bronner-Fraser

Early Regulatory Relationships in the Lamprey Neural Crest Gene Network

Nikitina N, Sauka-Spengler T, Bronner-Fraser M. Chapter 1. Gene regulatory networks in neural crest development and evolution. Curr Top Dev Biol. 2009;86:1-14.

Nikitina N, Sauka-Spengler T, Bronner-Fraser M. Dissecting early regulatory relationships in the lamprey neural crest gene network. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20083-8.

Sauka-Spengler T, Meulemans D, Jones M, Bronner-Fraser M. Ancient evolutionary
origin of the neural crest gene regulatory network. Dev Cell. 2007 Sep;13(3):405-20.

Hu N, Strobl-Mazzulla P, Sauka-Spengler T, Bronner ME. DNA methyltransferase3A as a molecular switch mediating the neural tube-to-neural crest fate transition. Genes Dev. 2012 Nov 1;26(21):2380-5.

Question 1

Very briefly tell us a bit about yourself, your career path over the years, and specifically what brought you to begin working on the evolution and development of neural crest cells?

Michael Barresi

Question 2

What are the evolutionary constraints that have kept organisms like the lamprey so similar to their ancestors that they can be used to study the evolution of processes such as neural crest development? How can you ensure that the lamprey shares enough similar characteristics as its ancestor to be used as an experimental system?

Michelle Deadwyler

Question 3

An essential point in the paper was that lamprey was a good model to use because it was a basal vertebrate and is comparable to its ancestor. However it is also mentioned that the parallel and redundant pathways that Zic A and Ap2 represent are there because of growing complexity of the organism and its gene regulatory network. Therefore, wouldn’t this show that this organism has become significantly different from that of its ancestor?

Amanda Smith

Question 4

In the 2008 paper’s discussion of AP-2 and ZicA as part of parallel pathways, it is suggested that functional redundancy of pathways in vertebrate GRNS is likely correlated with “developmental robustness of vertebrate embryos”. What does this “robustness” refer to?

Kristine Trotta

Question 5

And how is this fundamentally different from invertebrate embryological development? Would you expect less functional redundancy in invertebrate development, and why?

Lisa Friedman

Question 6

In the Bronner-Fraser (2008) article, AP-2 zebrafish mutants demonstrated no early role for this gene in neural crest specification. Do you think this is a characteristic of zebrafish alone, or a problem in translating the role of lamprey genes to higher species?

Stephanie Bond

Question 7

In your paper you state that it is not clear whether AP-2 activates Msc4 expression at the border or vice versa. In Ap-2 morphants, MsxA transcripts are lost in the neural plate border, but not in the noneural ectoderm. Do you think though, that MsxA transcript from the nonneural ectoderm could induce AP-2 to then regulate MsxA in the neural plate border?

Diane Chen

Question 8

You analyzed changing neural plate border specifiers and neural crest specifiers but do you think other components of the neural tube fusion have also changed? Like have there been changes in Cadherin expression too, or do you think the mechanisms of neural tube closure are more conserved?

Blair Bell

Question 9

From what we’ve learned in class, neural crest cells adopt different cell fates as they migrate and encounter different paracrine molecules. Have you considered what potential differences in the environmental signals exist between species and how that might impact neural crest specification?

Hailun Li

Question 10

In your most recent paper, you suggest that “DNMT3A might be recruited to the Sox2 promoter by some factors that are selectively expressed in the neural crest-forming domain.” What research has recently been done in this direction and what are your ideas as to how DNMT3A is recruited?

Elizabeth Summer

Question 11

Methyl transferases are frequently influenced by environmental factors. Do you think DNTM3A might be affected by fetal environment? Do you know of any environmental factors that may play a role in DNTM3A regulation? What might the mechanism of such regulation be?

Lydia-Rose Kesich