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Shaping skeletal growth by modular regulatory elements in the Bmp5 gene
Catherine Guenther1, Luiz Pantalena-Filho, David M Kingsley
1Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.
Plos Genetics
|December 20, 2008
Summary
Specific gene enhancers control the precise growth of individual bones and cartilage. This study reveals that distinct regulatory DNA sequences dictate skeletal morphology in different locations, offering insights into vertebrate anatomical diversity.
Area of Science:
- Developmental Biology
- Genomics
- Evolutionary Biology
Background:
- Vertebrate skeletal diversity arises from complex morphological blueprints encoded in the genome.
- Genomic mechanisms controlling precise skeletal growth patterns remain largely unknown.
- Bone Morphogenetic Protein 5 (Bmp5) is crucial for skeletal feature development.
Purpose of the Study:
- To identify the regulatory architecture controlling the developmental expression of the mouse Bmp5 gene.
- To investigate how enhancers regulate Bmp5 expression in specific skeletal locations.
- To understand the role of enhancers in controlling localized skeletal growth.
Main Methods:
- Large-scale enhancer surveys in mice.
- Analysis of Bmp5 gene expression patterns.
- Utilizing transgenic, null, and regulatory mutations.
- Investigating enhancer function in ribs and nasal cartilages.
Main Results:
- Bmp5 expression is controlled by different enhancers in individual bones.
- Distinct enhancers regulate Bmp5 expression in highly specific spatial subdomains on skeletal structures.
- Anatomy-specific enhancers are sufficient to alter skeletal morphology and control growth rates locally.
- These enhancers are essential for normal growth rates on separate bone surfaces.
Conclusions:
- Individual bones are composite structures with growth patterns determined by multiple lineage and gene expression domains.
- BMP gene enhancers provide a genomic mechanism for regulating precise growth domains in cartilage and bone.
- This regulatory control allows for the fine-tuning of skeletal anatomy at specific body locations.
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