Presentation on theme: "3D Substitution Model for Limb Growth and Pattern Formation Ying Zhang 1, Stuart A. Newman 2, James A. Glazier 1 1.Biocomplexity Institute, Department."— Presentation transcript:
3D Substitution Model for Limb Growth and Pattern Formation Ying Zhang 1, Stuart A. Newman 2, James A. Glazier 1 1.Biocomplexity Institute, Department of Physics, Indiana University 2.New York Medical College
: Substitution model
Tetsuya Tabata, et al. Nature, 2001 Patterning a Developmental Field by Long-range Signalling
Mechanisms of pattern formation in development and evolution Salazar-Ciudad I et al. Development 2003 I
Relation: Embryonic Development & Substitution Model Cellular autonomy Neighbor independent substitution system Example: cell growth, cell differentiation Cell signaling relay, cell-cell interaction model neighbor-dependent substitution model Example: cell-cell adhesion, cell sorting, cell migration, cell growth and death Positional information/Morphogenesis field theory Probability substitution model Example: FGF
Development of Limb Bud Newman SA. et al. Science 1979Gilbert et al 2003
FGFs & FGFRs Xu X. et al. Cell Tissue Res. 1999
Hox Gene Expression Nelson et al. Development 1996
Expansion of Cell Populations Vargesson N. et al. Development, 1997
Niswander, L. et al. Nature Reviews 2003 FGF ---outgrowth of the limb bud BMP--- Cartilage formation & Cell Death SHH Gli3Patterning SHH->HOXPatterning Gene Regulatory Network Gene & Function
Growth Rule && Growth Probability Field Division Differentiation Condensation Growth Probability Field
2D Subsitution Model Shubin et al. 1986
3D Substitution Simulation With Physical Branching and Differentiation rule
Fate Mapping Vargesson N. et al. Development, 1997
Morphogen Gradient Field Example:SHH-Gli3 Reaction Diffusion Oscillation or no Oscillation
Activator Inhibitor With Different Activator strength, form different Pattern Initial AS=2.9 AS=2.0
Fate Map Methods
Limb Bud Outgrowth
Summary 1. The substitution system is a suitable tool to enumerate growth process in embryonic development. 2.The substitution system as applied here can simulate real biological process, like cell division and differentiation. 3. Global behavior can be described by probability fields, which can link the molecular- signaling level to the cellular level. 4. Under certain growth probabilities to, the cell motion is still random according to fate map test.
Future Work Find out the suitable growth probability function. Implement the molecular information into the model. Application in other developmental system. Explore random/robustness effects in embryonic development. Explore surface tension constraints using the Cellular Potts model.
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