Evolutionary conservation, developmental expression, and genomic mapping of mammalian Twisted gastrulation

Graf, Daniel; Pm, Timmons; Hitchins, Megan P.; Episkopou,; Moore, GE; T, Ito; Fujiyama, Asao; Ag, Fisher; Merkenschlager, Matthias

doi:10.1007/s0033501-0005-x

Cited by 23 publications

(30 citation statements)

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“…47 BMP7 is produced by the distal tubule and collecting duct, 11,19 whereas CHRDL1 is secreted by the adjacent proximal tubule (Figures 2 and 3), establishing opposing gradients of these two proteins. Both in situ hybridization 20,35 and immunostaining ( Figure 4E) assays indicate that Twsg1 is expressed in the renal epithelia. Thus, it is anticipated that the proximal tubule of the healthy kidney is subject to the greatest BMP7 antagonism by CHRDL1/ TWSG1.…”

Section: Discussionmentioning

confidence: 94%

“…Previous studies showed ubiquitous Twsg1 expression in the kidney, with the highest expression in outer medulla. 20,35 TWSG1 protein expression was confirmed by immunostaining in both mouse and human kidney. In both species, protein expression is strong in proximal and other tubule epithelia and weak in interstitial cells and glomeruli ( Figure 4E).…”

Section: Chrdl1 Alone Amplifies Bmp4 and 7 Signaling But Selectively mentioning

confidence: 86%

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Chordin-like 1 and Twisted Gastrulation 1 Regulate BMP Signaling following Kidney Injury

Larman

Karolak²,

Adams³

et al. 2009

Journal of the American Society of Nephrology

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Stimulation of the bone morphogenetic protein (BMP) pathway protects the kidney from acute and chronic injury. Numerous regulators in the kidney control BMP signaling, offering many targets for therapeutic manipulation. Here, we screened for modulators of BMP signaling in the ischemia-sensitive S3 segment and found that Chordin-like 1 is expressed in this segment of both the mouse and human nephron. Chordin-like 1 specifically antagonizes BMP7, which is expressed in the neighboring distal nephron, and this depends on the presence of the protein Twisted gastrulation. Upon ischemia-induced degeneration of the S3 segment, we observed a reduction in Chordin-like 1 expression coincident with intense BMP signaling in tubules of the recovering kidney. Restored expression accompanied proximal tubule epithelia redifferentiation, again coincident with decreased BMP signaling. We propose that Chordin-like 1 reduces BMP7 signaling in healthy proximal tubules, and the loss of this activity upon sloughing of injured epithelia promotes BMP7 signaling in repopulating, dedifferentiated epithelia. As regenerating epithelia differentiate, Chordin-like 1 is again expressed, antagonizing BMP7. These data suggest a mechanism for dynamic regulation of renoprotective BMP7 signaling in the S3 segment of the proximal tubule.

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Section: Discussionmentioning

confidence: 94%

Section: Chrdl1 Alone Amplifies Bmp4 and 7 Signaling But Selectively mentioning

confidence: 86%

Chordin-like 1 and Twisted Gastrulation 1 Regulate BMP Signaling following Kidney Injury

Larman

Karolak²,

Adams³

et al. 2009

Journal of the American Society of Nephrology

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“…The twisted gastrulation (tsg ) invertebrate gene (Mason et al, 1994) has an equivalent gene family in vertebrates (mammalian tsg ) (Graf et al, 2001). Recently we investigated the expression of CCN3 during early embryogenesis (Katsube et al, 2001).…”

Section: Novel Ccn Molecules Which Regulate Notch Signaling Were Creamentioning

confidence: 99%

Notch in vertebrates - molecular aspects of the signal

Katsube

Sakamoto²

2005

Int. J. Dev. Biol.

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Notch is a receptor consisting of a single path transmembrane protein which is essential for stem cell regulation in both vertebrates and invertebrates. We have investigated the function of Notch signaling and found that ligands of the Notch receptor (Delta and Serrate) sometimes act as receptor modulators in a cell autonomous manner; the balance of their activity as ligands explains satisfactorily 'lateral inhibition' as well as 'lateral specification'. This model explains not only fly morphogenesis, but also the general regulation of stem cells. In vertebrates, members of a novel family of genes which encode small secretory proteins, CCN, were demonstrated to bind to Notch and stimulate signaling. This is not a ligand type binding, but rather a modifier of the protein structure of Notch, so as to form a macromolecular complex. This association may open up novel perspectives on Notch signaling, for instance in the movement of cells involved in somite segmentation or angiogenesis. Thus, a well-conserved signal such as Notch seems to have changed in function during the evolution of vertebrates.

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“…Mouse Tsg is expressed during lymphocyte development (22), and Chordin (23), BMP4 (24), and the Smad-interacting transcription factor Schnurri-2 (25) are expressed in the mouse thymus, suggesting that BMP signaling may play a role in thymocyte development.…”

mentioning

confidence: 99%

Bone Morphogenetic Protein 2/4 Signaling Regulates Early Thymocyte Differentiation

Hager-Theodorides

Outram

Shah

et al. 2002

The Journal of Immunology

111

131

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Bone morphogenetic protein (BMP)2 and BMP4 are involved in the development of many tissues. In this study, we show that BMP2/4 signaling is involved in thymocyte development. Our data suggest that termination of BMP2/4 signaling is necessary for differentiation of CD44+CD25−CD4−CD8− double negative (DN) cells along the T cell lineage. BMP2 and BMP4 are produced by the thymic stroma and the requisite BMP receptor molecules (BMPR-1A, BMPR-1B, BMPR-II), and signal transduction molecules (Smad-1, -5, -8, and -4) are expressed by DN thymocytes. BMP4 inhibits thymocyte proliferation, enhances thymocyte survival, and arrests thymocyte differentiation at the CD44+CD25− DN stage, before T cell lineage commitment. Neutralization of endogenous BMP2 and BMP4 by treatment with the antagonist Noggin promotes and accelerates thymocyte differentiation, increasing the expression of CD2 and the proportion of CD44−CD25− DN cells and CD4+CD8+ double-positive cells. Our study suggests that the BMP2/4 pathway may function in thymic homeostasis by regulating T cell lineage commitment and differentiation.

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Evolutionary conservation, developmental expression, and genomic mapping of mammalian Twisted gastrulation

Cited by 23 publications

References 0 publications

Chordin-like 1 and Twisted Gastrulation 1 Regulate BMP Signaling following Kidney Injury

Chordin-like 1 and Twisted Gastrulation 1 Regulate BMP Signaling following Kidney Injury

Notch in vertebrates - molecular aspects of the signal

Bone Morphogenetic Protein 2/4 Signaling Regulates Early Thymocyte Differentiation

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