The neural crest is a population of migratory stem cells that contributes extensively to development of many of the structures that define vertebrates, including the jaw. Because the neural crest is important both in vertebrate development and in vertebrate evolutionary origins it has been the subject of intense study for decades. It is now well accepted that a cascading network of regulatory molecules collectively known as the neural-crest gene regulatory network commits progenitor cells to the neural-crest fate, and that disruption of this network grossly perturbs development of the animal. It is known that multiple transcription factors and chromatin-modifying proteins, which are two categories of genetic regulatory molecule, contribute to the network. However, the specific interactions among these regulatory molecules remain poorly understood.

This question will be tackled using genetic approaches in zebrafish embryos. Embryonic development in zebrafish, as all vertebrates, depends on the neural crest. Zebrafish embryos develop externally of the mother and are transparent. These features make them particularly well suited to investigations of mechanisms of embryonic development shared by all vertebrates.

At the conclusion of this work, an understanding of how each of these regulatory molecules fits within the neural crest gene regulatory network will be gained, as well as knowledge of the order of function of each protein and of the nature of the regulatory interactions, i.e. activating or inhibiting, to which they contribute. An understanding of how a transcription factor that is required in multiple cell types is directed to neural-crest specific targets by a chromatin-modifying protein should also be advanced. The potential impact of this work is a profoundly improved understanding of the genetic mechanisms governing neural crest development and vertebrate evolutionary origins. This work will provide training in cutting-edge molecular genetic methods for students from under represented minorities, and includes outreach at local public schools.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Application #
1147221
Program Officer
Steven Klein
Project Start
Project End
Budget Start
2012-02-01
Budget End
2017-01-31
Support Year
Fiscal Year
2011
Total Cost
$822,962
Indirect Cost
Name
University of Iowa
Department
Type
DUNS #
City
Iowa City
State
IA
Country
United States
Zip Code
52242