A Somitic Compartment of Tendon Progenitors

Brent, Ava E.; Schweitzer, Ronen; Tabin, Clifford J.

doi:10.1016/s0092-8674(03)00268-x

Cited by 478 publications

(554 citation statements)

References 32 publications

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“…We identified this clone as the cDNA that encodes Scx using the RACE method. Scx was originally identified as a bHLH transcription factor that is expressed in the sclerotome, in mesenchymal precursors of bone and cartilage, and in connective tissues (33,34). From these reports, Scx has been implicated in the regulation of the development of collagenrich tissues such as tendons and ligaments.…”

Section: Tgf␤1-induced Sma Expression Besides Activation Of Smad3 In mentioning

confidence: 99%

Scleraxis Modulates Bone Morphogenetic Protein 4 (BMP4)-Smad1 Protein-Smooth Muscle α-Actin (SMA) Signal Transduction in Diabetic Nephropathy

Abe

Tominaga

Matsubara

et al. 2012

Journal of Biological Chemistry

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Background: Activated mesangial cells exhibit SMA and contribute to the progression of diabetic nephropathy. Results: Scleraxis negatively regulated the AGE-induced expression and secretion of BMP4. Conclusion: Scleraxis and Id1 are involved in the BMP4-SMA pathway and modulate phenotypic changes. Significance: Deeper insight into the impact of regulatory mechanism of scleraxis-BMP4-Smad1 signal activation might help to prevent diabetic glomerular damage.

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Section: Tgf␤1-induced Sma Expression Besides Activation Of Smad3 In mentioning

confidence: 99%

Scleraxis Modulates Bone Morphogenetic Protein 4 (BMP4)-Smad1 Protein-Smooth Muscle α-Actin (SMA) Signal Transduction in Diabetic Nephropathy

Abe

Tominaga

Matsubara

et al. 2012

Journal of Biological Chemistry

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“…The regulation of tendon formation during development is largely unknown (reviewed in Edom-Vovard and Duprez, 2004;Tozer and Duprez, 2005). Only in recent years has a highly specific marker for tendons, basic helix-loophelix transcription factor scleraxis, been identified (Schweitzer et al, 2001;Brent et al, 2003). The function of scleraxis during tendon development has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal protein distribution of TGF‐βs, their receptors, and extracellular matrix molecules during embryonic tendon development

Kuo

Petersen

Tuan

2008

Developmental Dynamics

109

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Tendon is one of the least understood tissues of the musculoskeletal system in terms of development and morphogenesis. Collagen fibrillogenesis has been the most studied aspect of tendon development, focusing largely on the role of matrix molecules such as collagen type III and decorin. While involvement of matrix molecules in collagen fibrillogenesis during chick tendon development is well understood, the role of growth factors has yet to be elucidated. This work examines the expression patterns of transforming growth factor (TGF) -␤1, -␤2, and -␤3, and their receptors with respect to expression patterns of collagen type III, decorin, and fibronectin. We focus on the intermediate stages of tendon development in the chick embryo, a period during which the tendon micro-and macro-architecture are being established. Our findings demonstrate for the first time that TGF-␤1, -␤2, and -␤3 have distinct spatiotemporal developmental protein localization patterns in the developing tendon and strongly suggest that these isoforms have independent roles in tendon development.

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“…Scleraxis is required for mesoderm formation during gastrulation (59). Later during embryogenesis, scleraxis is expressed in mesenchymal precursors of the axial and appendicular skeleton and tendons (29,66,67). Scleraxis has been shown to act as a transcriptional activator by binding to E-box sequences as a heterodimer with E proteins.…”

Section: Discussionmentioning

confidence: 99%

Paraxis Is a Basic Helix-Loop-Helix Protein That Positively Regulates Transcription through Binding to Specific E-box Elements

Wilson‐Rawls

Rhee

Rawls

2004

Journal of Biological Chemistry

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Members of the Twist subfamily of basic helix-loophelix transcription factors are important for the specification of mesodermal derivatives during vertebrate embryogenesis. This subfamily includes both transcriptional activators such as scleraxis, Hand2, and Dermo-1 and repressors such as Twist and Hand1. Paraxis is a member of this subfamily, and it has been shown to regulate morphogenetic events during somitogenesis, including the transition of cells from mesenchyme to epithelium and maintaining anterior/posterior polarity. Mice deficient in paraxis exhibit a caudal truncation of the axial skeleton and fusion of the vertebrae. Considering the developmental importance of paraxis, it is important for future studies to understand the molecular basis of its activity. Here we demonstrate that paraxis can function as a transcriptional activator when it forms a heterodimer with E12. Paraxis is able to bind to a set of E-boxes that overlaps with the closely related scleraxis. Paraxis expression precedes that of scleraxis in the region of the somite fated to form the axial skeleton and tendons and is able to direct transcription from an E-box found in the scleraxis promoter. Further, in the absence of paraxis, Pax-1 is no longer expressed in the somites and presomitic mesoderm. These results suggest that paraxis may regulate early events during chondrogenesis by positively directing transcription of sclerotome-specific genes.The basic helix-loop-helix (bHLH) 1 superfamily of transcription factors regulates a wide array of developmental processes, including neurogenesis, myogenesis, cardiogenesis, hematopoiesis, and gametogenesis (1-8). The bHLH transcription factors belong to a larger superfamily of helix-loop-helix transcription factors that contains more than 240 proteins that are expressed in eukaryotic organisms that range from yeast to humans (9). Members of this family possess a highly conserved functional domain containing a stretch of basic amino acids adjacent to two amphipathic ␣-helices separated by a loop (10). The helices mediate dimerization with a second bHLH factor, bringing the basic domains into close proximity and forming the bipartite DNA binding domain. The bHLH dimers bind specifically to a hexanucleotide sequence (CANNTG), known as an E-box (11). E-boxes are found in the control regions of many lineage-specific genes. In some cases, such as the muscle-specific genes myogenin, myosin light chain, and muscle creatine kinase, the E-box is required for full transcription of the gene (12-16).The bHLH proteins can be divided into two classes based on tissue distribution and dimerization capabilities. Class A bHLH factors are known as E proteins and include the E2A gene products E12 and E47, HEB, and the Drosophila daughterless gene product (17, 18). These genes are broadly expressed and able to form homo-and heterodimers. Class B bHLH factors exhibit tissue-restricted expression patterns (19,20). Within this class are both transcriptional activators, such as MyoD and MashI, and transcriptional represso...

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A Somitic Compartment of Tendon Progenitors

Cited by 478 publications

References 32 publications

Scleraxis Modulates Bone Morphogenetic Protein 4 (BMP4)-Smad1 Protein-Smooth Muscle α-Actin (SMA) Signal Transduction in Diabetic Nephropathy

Scleraxis Modulates Bone Morphogenetic Protein 4 (BMP4)-Smad1 Protein-Smooth Muscle α-Actin (SMA) Signal Transduction in Diabetic Nephropathy

Spatiotemporal protein distribution of TGF‐βs, their receptors, and extracellular matrix molecules during embryonic tendon development

Paraxis Is a Basic Helix-Loop-Helix Protein That Positively Regulates Transcription through Binding to Specific E-box Elements

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