Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development

Zakin, Lise; Robertis, Edward M. De

doi:10.1242/dev.00946

Cited by 73 publications

(102 citation statements)

References 76 publications

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“…Our result indicates that this inhibition must be enhanced by the presence of Tsg. Recent results from Tsg-deficient mice indicated a critical role of Tsg in skeletal development of vertebrates (47)(48)(49)(50). Tsg has also been shown to be an important modulator of BMP-regulated cartilage development and chondrocyte differentiation (51).…”

Section: Discussionmentioning

confidence: 99%

von Willebrand Factor Type C Domain-containing Proteins Regulate Bone Morphogenetic Protein Signaling through Different Recognition Mechanisms

Zhang

Huang

Qiu

et al. 2007

Journal of Biological Chemistry

130

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Section: Discussionmentioning

confidence: 99%

von Willebrand Factor Type C Domain-containing Proteins Regulate Bone Morphogenetic Protein Signaling through Different Recognition Mechanisms

Zhang

Huang

Qiu

et al. 2007

Journal of Biological Chemistry

130

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“…However, a group of genes involved in cardiac development (Gata4 (Kuo et al 1997, Tevosian et al 2002, Adam19 (Kurohara et al 2004), Fgf4, and Fgfr2 (Feldman et al 1995, Wang et al 2005, and Bmp4 (Liu et al 2004, Zakin & De Robertis 2004 are down- Effect of IVF on mouse preimplantation embryo regulated, and Cebpa knock outs show abnormalities in adipogenesis, hematopoiesis, hepatic, and lung morphology and premature death (Flodby et al 1996, Zhang et al 2004. It is possible that these changes are temporary and disappear, but could persist and affect long term development, extending the Barker hypothesis (Barker 1998) to the preimplantation period.…”

Section: Discussionmentioning

confidence: 99%

Effect of in vitro fertilization on gene expression and development of mouse preimplantation embryos

Giritharan¹,

Talbi²,

Donjacour³

et al. 2007

Reproduction

141

127

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In vitro culture (IVC) of preimplantation mouse embryos is associated with changes in gene expression. It is however, not known if the method of fertilization affects the global pattern of gene expression. We compared gene expression and development of mouse blastocysts produced by in vitro fertilization (IVF) versus blastocysts fertilized in vivo and cultured in vitro from the zygote stage (IVC) versus control blastocysts flushed out of the uterus on post coital day 3.5. The global pattern of gene expression was assessed using the Affymetrix 430 2.0 chip. It appears that each method of fertilization has a unique pattern of gene expression and development. Embryos cultured in vitro had a reduction in the number of trophoblastic cells (IVF 33.5 cells, IVC 39.9 cells, and 49.6 cells in the in vivo group) and, to a lesser degree, of inner cell mass cells (12.8, 11.7, and 13.8 respectively). The inner cell mass nuclei were larger after culture in vitro (140 mm 2 , 113 mm 2 , and 86 mm 2 respectively). Although a high number of genes (1912) was statistically different in the IVF cohort when compared with the in vivo control embryos, the magnitude of the changes in gene expression were low and only a minority of genes (29 genes) was changed more than fourfold. Surprisingly, IVF embryos were different from IVC embryos (3058 genes were statistically different, but only three changed more than fourfold). Proliferation, apoptosis, and morphogenetic pathways are the most common pathways altered after IVC. Overall, IVF and embryo culture have a profound effect on gene expression pattern and phenotype of mouse preimplantation embryos.

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“…In the early mouse embryo, TSG is expressed in extraembryonic tissues, branchial arches, neural ectoderm, prechondrogenic mesoderm, intercostal vascular bundles, and other tissues (35,39). In later stages at E15.5-17.5, TSG has been identified in the digital rays and the joint surfaces (35).…”

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confidence: 99%

Twisted Gastrulation Modulates Bone Morphogenetic Protein-induced Collagen II and X Expression in Chondrocytesin Vitroandin Vivo

et al. 2006

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Twisted gastrulation (TSG) is an extracellular modulator of bone morphogenetic protein (BMP) activity and regulates dorsoventral axis formation in early Drosophila and Xenopus development. Studies on tsg-deficient mice also indicated a role of this protein in skeletal growth, but the mechanism of TSG activity in this process has not yet been investigated. Here we show for the first time by in situ hybridization and immunohistochemistry that TSG is strongly expressed in bovine and mouse growth plate cartilage as well as in fetal ribs, vertebral cartilage, and cartilage anlagen of the skull. Furthermore we provide evidence that TSG is directly involved in BMP-regulated chondrocyte differentiation and maturation. In vitro, TSG impaired the dose-dependent BMP-2 stimulation of collagen II and X expression in cultures of MC615 chondrocytes and primary mouse chondrocytes. In the presence of chordin, a BMP antagonist, the inhibitory effect of TSG was further enhanced. TSG also inhibited BMP-2-stimulated phosphorylation of Smad factors in chondrocytes, confirming the role of TSG as a modulator of BMP signaling. For analysis of TSG functions in cartilage development in vivo, the gene was overexpressed in transgenic mice under the control of the cartilage-specific Col2a1 promoter. As a result, Col10a1 expression was significantly reduced in the growth plates of transgenic embryos and newborns in comparison with wild type littermates as shown by in situ hybridization and by real time PCR analysis. The data suggest that TSG is an important modulator of BMP-regulated cartilage development and chondrocyte differentiation.Bone morphogenetic proteins (BMPs) 5 are key regulators in the formation of cartilage models of vertebrate long bones, vertebrae, and ribs and their transition to bone during endochondral ossification (for reviews, see Refs. 1-5). However, the role of BMP factors in cartilage development and chondrocyte differentiation is complex and differs with time and site of chondrogenic differentiation: BMPs control limb outgrowth by negatively modulating apical ectodermal ridge activity (6 -8), whereas BMPs are required for the formation of prechondrogenic mesenchyme and chondrocyte differentiation in the limb (9). The ability of BMP-2, BMP-4, and others to induce chondrogenic differentiation of undifferentiated stems cells in vivo and in vitro has been amply demonstrated (10 -12). In line with this observation is the finding that chondrogenesis in vivo is impaired by blocking BMP activities with noggin (13, 14) or deletion of the BMP receptor (BMPRIB) (15).The role of BMPs during chondrocyte maturation and hypertrophy is also complex and controversially discussed: several studies show that BMP factors such as BMP-6 and BMP-7 stimulate hypertrophic differentiation of chondrocytes and promote collagen X expression (16 -18), thus preparing growth plate cartilage for replacement by endochondral bone. On the other hand, it was reported that BMP-2 and BMP-4 overexpression in developing chick limbs caused delayed hypertroph...

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Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development

Cited by 73 publications

References 76 publications

von Willebrand Factor Type C Domain-containing Proteins Regulate Bone Morphogenetic Protein Signaling through Different Recognition Mechanisms

von Willebrand Factor Type C Domain-containing Proteins Regulate Bone Morphogenetic Protein Signaling through Different Recognition Mechanisms

Effect of in vitro fertilization on gene expression and development of mouse preimplantation embryos

Twisted Gastrulation Modulates Bone Morphogenetic Protein-induced Collagen II and X Expression in Chondrocytesin Vitroandin Vivo

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