A minimally sufficient model for rib proximal-distal patterning based on genetic analysis and agent-based simulations
Abstract
For decades, the mechanism of skeletal patterning along a proximal-distal axis has been an area of intense inquiry. Here we examine the development of the ribs, simple structures that in most terrestrial vertebrates consist of two skeletal elements- a proximal bone and a distal cartilage portion. While the ribs have been shown to arise from the somites, little is known about how the two segments are specified. During our examination of genetically modified mice, we discovered a series of progressively worsening phenotypes that could not be easily explained. Here, we combine genetic analysis of rib development with agent-based simulations to conclude that proximal-distal patterning and outgrowth could occur based on simple rules. In our model, specification occurs during somite stages due to varying Hedgehog protein levels, while later expansion refines the pattern. This framework is broadly applicable for understanding the mechanisms of skeletal patterning along a proximal-distal axis.
Article and author information
Author details
Funding
California Institute for Regenerative Medicine (Postdoctoral Fellowship)
- Jennifer L Fogel
University of Southern California
- Jennifer L Fogel
- Daniel L Lakeland
- In Kyoung Mah
- Francesca V Mariani
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#11152) of the University of Southern California.
Copyright
© 2017, Fogel et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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