Estimating the spatiotemporal pattern of volumetric growth rate from fate maps in chick limb development

Morishita, Yoshihiro; Iwasa, Yoh

doi:10.1002/dvdy.21840

Cited by 2 publications

(1 citation statement)

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“…Since limb bud shape is controlled by a different set of molecular determinants from the ones regulating the initiation of chondrogenesis (reviewed in ref. [2]), a more complete model would incorporate an independent system of equations for limb bud shaping [64], [65] involving the growth [66] and viscoelastic [67] properties of the limb bud tissue regulated by molecules such as Wnt, Shh, Gli3, and FGFs [68], [69].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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

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Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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Computational and mathematical models of chondrogenesis in vertebrate limbs

Glimm

Headon

Kiskowski

2012

Birth Defects Research Pt C

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The production of cartilage (chondrogenic patterning) in the limb is one of the best-studied examples of the emergence of form in developmental biology. At the core of the theoretical study is an effort to understand the mechanism that establishes the characteristic distribution of cartilage in the embryonic limb, which defines the future sites and shapes of bones that will be present in the mature limb. This review article gives an overview of the history and current state of a rich literature of mathematical and computational models that seek to contribute to this problem. We describe models for the mechanisms of limb growth and shaping via interaction with various chemical fields, as well as models addressing the intrinsic self-organization capabilities of the embryonic mesenchymal tissue, such as reaction-diffusion and mechanochemical models. We discuss the contributions of these models to the current understanding of chondrogenesis in vertebrate limbs, as well as their relation to the varied conceptual models that have been proposed by experimentalists.

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Estimating the spatiotemporal pattern of volumetric growth rate from fate maps in chick limb development

Cited by 2 publications

References 36 publications

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

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

Computational and mathematical models of chondrogenesis in vertebrate limbs

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