A fundamental question in biology is how development of the elaborately organized mammalian brain is orchestrated. Current knowledge suggests that the pattern formation during brain development is guided by a variety of signals including diffusible neurotrophic factors and preformed distributions of extracellular matrix proteins including adhesion molecules. The relative contributions of these elements and the number of permutations of each type of signal is unknown. To develop a better understanding of the movement and differentiation of neural stem cells (NSCs) in vivo, we propose to develop a mathematical model, using a cell culture system to provide quantitative data for the model. We will test the hypothesis that individual cells in a NSC population are diverse in their capability of responding to their environment by migration and differentiation. As a corollary to this hypothesis, we will test whether NSCs respond with different behaviors to unique combinations of signals from diffusible neurotrophic factors and preformed distributions of extracellular matrix (ECM) proteins. Based on this hypothesis, we propose the following specific aims: 1) Develop a biological model to test the role of extracellular matrix proteins and diffusible factors on NSC patterning. 2) Develop a mathematical model that can predict the outcome of perturbations in the biological model, and 3) Test the mathematical model using an organ culture system for NSC patterning. The current team is well prepared to carry out the proposed project and includes a developmental biologist, a molecular biologist, a polymer chemist, a mathematician, and a numerical modeler. Several individuals in this group have collaborated for many years and the group met and discussed this problem over the period of a year before submitting the application. This interdisciplinary approach will provide fundamental insights into the process of stem cell behavior during tissue integration. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM072005-03
Application #
7060780
Study Section
Special Emphasis Panel (ZGM1-CMB-0 (MB))
Program Officer
Whitmarsh, John
Project Start
2004-05-01
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$287,156
Indirect Cost
Name
Iowa State University
Department
Biochemistry
Type
Schools of Earth Sciences/Natur
DUNS #
005309844
City
Ames
State
IA
Country
United States
Zip Code
50011
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