An Emerging Regulatory Landscape for Skeletal Development. Issue 12 (December 2016)

• Record Type: Journal Article
• Authors: Hojo, Hironori; McMahon, Andrew P.; Ohba, Shinsuke
• Is Part Of: Trends in genetics. Volume 32:Issue 12(2016)
• Page Start: 774
• Page End: 787
• Publication Date: 2016-12
• Subjects: cell specification -- chondrocytes -- gene regulatory networks -- osteoblast -- skeletal development -- transcriptional regulators; Genetics -- Periodicals; 576.5
• DOI: 10.1016/j.tig.2016.10.001
• Languages: English
• ISSNs: 0168-9525

Abstract

Abstract : Skeletal development creates the physical framework that shapes our body and its actions. In the past two decades, genetic studies have provided important insights into the molecular processes at play, including the roles of signaling pathways and transcriptional effectors that coordinate an orderly, progressive emergence and expansion of distinct cartilage and bone cell fates in an invariant temporal and spatial pattern for any given skeletal element within that specific vertebrate species. Genome-scale studies have provided additional layers of understanding, moving from individual genes to the gene regulatory landscape, integrating regulatory information through cis -regulatory modules into cell type-specific gene regulatory programs. This review discusses our current understanding of the transcriptional control of mammalian skeletal development, focusing on recent genome-scale studies. Trends: Recent progress afforded by genome-scale studies has provided new insights into the actions of key transcriptional regulators in the epigenetic landscape regulating mammalian skeletal development. ChIP-seq analyses for skeletal cell determinants including Sox9, Runx2, and Sp7 identified their putative targets and modes of action in chondrocytes and osteoblasts. Other genome-scale studies have revealed the molecular link between the determinants at the single-cell level. Integrative analyses with these genome-scale data will be the key to learning spatial-, temporal- and cell type-distinct signatures (which represent the nature of skeletal development) and to gaining molecular-level insights into pathological mechanisms of skeletal diseases.