Signaling pathways in human skeletal dysplasias

Dustin Baldridge, Oleg Shchelochkov, Brian Kelley, Brendan Lee

Research output: Contribution to journalReview articlepeer-review

47 Scopus citations


Human skeletal dysplasias are disorders that result from errors in bone, cartilage, and joint development. A complex series of signaling pathways, including the FGF, TGFβ, BMP, WNT, Notch, and Hedgehog pathways, are essential for proper skeletogenesis, and human skeletal dysplasias are often a consequence of primary or secondary dysregulation of these pathways. Although these pathways interact to regulate bone, cartilage, and joint formation, human genetic phenotypes point to the predominant action of specific components of these pathways. Mutations in the genes with a role in metabolic processing within the cell, the extracellular matrix, and transcriptional regulation can lead to dysregulation of cell-cell and cell-matrix signaling that alters tissue patterning, cell differentiation, proliferation, and apoptosis. We propose a morphogen rheostat model to conceptualize how mutations in different metabolic processes can lead to the integration of differential signaling inputs within a temporal and spatial context to generate apparently divergent skeletal phenotypes.

Original languageEnglish
Pages (from-to)189-217
Number of pages29
JournalAnnual Review of Genomics and Human Genetics
StatePublished - Sep 22 2010


  • BMP
  • FGF
  • Notch
  • TGFβ
  • WNT
  • hedgehog


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