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Related Experiment Videos

Morphogenesis and dysmorphogenesis of the appendicular skeleton.

Lillian Shum1, Cynthia M Coleman, Yuji Hatakeyama

  • 1Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 50, Room 1503, MSC 8022, Bethesda, MD 20892, USA.

Birth Defects Research. Part C, Embryo Today : Reviews
|September 6, 2003
PubMed
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This review details cartilage development and endochondral ossification (EO) using limb bud development as a model. It explores molecular pathways, genetic mutations, and environmental factors causing skeletal birth defects.

Area of Science:

  • Developmental biology
  • Skeletal biology
  • Molecular genetics

Background:

  • Cartilage patterning and differentiation are crucial for skeletal development via endochondral ossification (EO).
  • Mesenchymal cells transform into chondrocytes through complex cell fate determination, requiring intricate cell-cell and cell-matrix interactions.

Purpose of the Study:

  • To review limb bud development as a model for understanding cartilage patterning and differentiation.
  • To summarize molecular and cellular events, signaling pathways, and factors influencing skeletal development and malformations.

Main Methods:

  • Review of existing literature on limb bud development.
  • Analysis of molecular and cellular events in cartilage development and EO.
  • Examination of genetic and teratogenic factors affecting skeletal formation.

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Main Results:

  • Limb bud development involves axis patterning, cell condensation, fate determination, digit formation, apoptosis, EO, and joint formation.
  • Interconnected pathways highlight how genetic (e.g., FGFR, GLI3, GDF5/CDMP1, Sox9, Cbfa1 mutations) and teratogenic factors (e.g., thalidomide, alcohol) cause skeletal birth defects.
  • Understanding these processes offers insights into normal cartilage biology, congenital disorders, and adult cartilage pathology.

Conclusions:

  • Cartilage development and EO are complex processes orchestrated by multiple signaling pathways.
  • Perturbations in these pathways, due to genetic or environmental factors, lead to significant skeletal malformations.
  • This review provides a comprehensive understanding of skeletal development, informing research on congenital disorders and cartilage diseases.