Abstract
Avian limb buds form primarily from a mixture of ectodermal and mesenchymal cells. The mesenchymal cells derive from two sources, the lateral plate mesoderm and the somites. Somite‐derived structures in mature limbs include muscles, tendons, and vascular endothelium. Limb development potentially shares many regulatory pathways and developmental mechanisms with somitogenesis, such as WNT and FGF8 regulation of cell proliferation, MET transitions, and differentiation. Although some mechanisms are likely to be conserved, tissue‐specific contextual cues are likely to introduce differences both significant and subtle. We present three‐dimensional, multi‐scale, multicell models using the open‐source CompuCell3D modeling environment to simulate these experimentally‐observed developmental mechanisms. We combine sub‐cellular (genetic and signaling networks), cellular (cell growth, death, division, differentiation and motility) and tissue (extracellular matrix and morphogen production) level scales to explore if combining WNT, FGF8 and Delta/Notch signaling (active during somitogenesis) with contact inhibition of growth in the ectoderm and the formation and maintenance of the Dorsal‐Ventral boundary at the apical ecotodermal ridge suffices to generate the unique patterning and growth dynamics of the limb bud. Supported by NIH 2R01GM076692–07and EPA R‐10–0049A3.Grant Funding Source: N/A
Published Version
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