Bare Bones Pattern Formation: A Core Regulatory Network in Varying Geometries Reproduces Major Features of Vertebrate Limb Development and Evolution

• DOI: 10.1371/journal.pone.0010892
• Publication Date: 2010-05-28T20:49:30Z
• Authors: Jianfeng Zhu; Yong-Tao Zhang; Mark S. Alber; Stuart A. Newman
• Keywords: Limb bud; Limb development; Apical ectodermal ridge; Chondrogenesis; SOX9

Background Major unresolved questions regarding vertebrate limb development concern how the numbers of skeletal elements along proximodistal (P-D) and anteroposterior (A-P) axes are determined shape a growing affects element formation. There is currently no generally accepted model for these patterning processes, but recent work on cartilage (chondrogenesis) indicates that precartilage tissue self-organizes into nodular patterns by cell-molecular circuitry with local auto-activating lateral inhibitory (LALI) properties. This process played out in developing context gradient fibroblast growth factor (FGF) emanating from apical ectodermal ridge (AER). Results We have simulated behavior core chondrogenic mechanism presence an FGF using novel computational environment permits simulation LALI systems domains varying size. The predicts normal pattern skeletogenesis as well distal truncations resulting AER removal. Modifications model's parameters corresponding to plausible effects Hox proteins formins, reshaping limb, bud yielded phenotypes resembling mutational experimental variants limb. Hypothetical developmental scenarios reproduce morphologies features fossil limbs. Conclusions regulatory system operating has inherent, robust propensity form limb-like structures. bare bones framework can accommodate ancillary gene networks controlling shaping establishment expression domains. accounts major and, under variant geometries different parameter values, those experimentally manipulated, genetically aberrant evolutionary early forms, requirement independent positional information.