Get access

Transcriptional dysregulation in skeletal malformation syndromes


  • Pia Hermanns,

    Search for more papers by this author
    • Pia Hermanns is a Visiting Research Associate from the Department of Pediatrics at the University of Mainz. She has been focused on understanding the molecular events underlying chondrocyte differentiation and the associated pathological processes.

  • Brendan Lee

    Corresponding author
    • Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room 630E, Houston, TX 77030.
    Search for more papers by this author
    • Brendan Lee is Associate Professor in the Department of Molecular and Human Genetics at the Baylor College of Medicine and Director of the Skeletal Dysplasia Clinic at the Texas Children's Hospital. He has had a long-standing interest in the transcriptional regulation of skeletal morphogenesis and the consequences of dysregulation of these transcriptional networks.


Normal skeletal development requires coordinated temporal and spatial gene expression patterns that specify the functions of various cell types. Transcription factors by definition coordinate this process and are themselves subject to hierarchical levels of regulation. Together they determine the context-dependent function of each transcription factor. Hence, loss-of-function and gain-of-function mutations within specific transcription factors cause dysregulation of broad transcriptional networks. Consequences are usually dominantly inherited skeletal malformation syndromes that can be broadly viewed as consequences of defects of cellular differentiation, proliferation, and survival versus defects in pattern formation. The study of human phenotypes and mutations can lead to hypotheses about targets within the respective transcriptional network. These targets can then be confirmed by combining mouse genetic and in vitro studies. Although this has been successful in a small group of skeletal dysplasias, the majority of transcriptional networks during skeletogenesis remain to be elucidated. © 2002 Wiley-Liss, Inc.