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Related Concept Videos

Changes in the Appendicular Skeleton with Age01:09

Changes in the Appendicular Skeleton with Age

The upper and lower limb initially develops as a small bulge called a limb bud, which appears on the lateral side of the early embryo. The upper limb bud appears near the end of the fourth week of development, with the lower limb bud appearing shortly after.
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
Development of the Limb Synovial Joints01:07

Development of the Limb Synovial Joints

Joints form during embryonic development in conjunction with the formation and growth of the associated bones. The embryonic tissue that gives rise to all bones, cartilage, and connective tissues of the body is called mesenchyme.
The mesenchymal stem cells differentiate into chondrocytes that form the hyaline cartilage, and later the cartilaginous model of the bone. This model further transforms into a bone. This process is known as endochondral ossification.
During development, the limbs...
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
Bone Remodeling and Repair01:31

Bone Remodeling and Repair

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...
Bone Formation by Endochondral Ossification01:24

Bone Formation by Endochondral Ossification

Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...

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Chicken Recombinant Limbs Assay to Understand Morphogenesis, Patterning, and Early Steps in Cell Differentiation
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Making sense-data-based simulations of vertebrate limb development.

Dagmar Iber1, Rolf Zeller

  • 1Computational Biology, Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, CH-4058 Basel, Switzerland. dagmar.iber@bsse.ethz.ch

Current Opinion in Genetics & Development
|December 26, 2012
PubMed
Summary

Integrating mathematical models with experimental data enhances understanding of limb bud development. This systems biology approach allows for realistic simulations and predictions of gene interactions in organogenesis.

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Area of Science:

  • Developmental Biology
  • Systems Biology
  • Computational Biology

Background:

  • Limb bud development is crucial for vertebrate organogenesis, involving complex molecular and cellular mechanisms.
  • Despite extensive study, general regulatory paradigms governing limb bud organization remain poorly understood.
  • Mathematical theories for developmental processes often lack experimental validation.

Purpose of the Study:

  • To bridge the gap between theoretical models and experimental data in limb bud development.
  • To leverage systems biology approaches for a more integrated understanding of organogenesis.
  • To explore the potential of computational models for predicting developmental mechanisms.

Main Methods:

  • Interlinking experimental and mathematical approaches within a systems biology framework.
  • Utilizing molecular and genetic analysis for the experimental validation of computational models.
  • Refining mathematical simulations based on experimental feedback to increase realism.

Main Results:

  • Developed increasingly realistic computational models of limb bud development.
  • Identified inconsistencies in existing experimental data interpretations.
  • Demonstrated the predictive power of models for key regulatory interactions and core/accessory mechanisms.

Conclusions:

  • Integrative analysis of limb organogenesis supports the use of network simulations for in silico genetics.
  • Computational modeling enables the simulation of complex loss-of-function and gain-of-function states.
  • In silico genetics offers a powerful tool for studying phenotypes difficult to generate experimentally, advancing the study of vertebrate limb development.