The mouse rib-vertebrae mutation is a hypomorphic Tbx6 allele

Watabe-Rudolph, Masami; Schlautmann, Nicole; Papaioannou, Virginia E.; Gossler, Achim

doi:10.1016/s0925-4773(02)00394-5

Cited by 66 publications

(58 citation statements)

References 31 publications

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“…rv is a hypomorphic allele of the Tbx6 gene (Watabe-Rudolph et al 2002), which encodes a T-box transcription factor specifically expressed in the primitive streak/tailbud and presomitic mesoderm (Chapman et al 1996). To address how the complete loss of Tbx6 function affects Dll1, we analyzed Dll1 expression in embryos carrying a targeted null allele of Tbx6.…”

Section: Resultsmentioning

confidence: 99%

“…Further support for this idea comes from our analysis of the mouse rib-vertebrae (rv) mutation, which represents a hypomorphic Tbx6 allele causing reduced Tbx6 expression (Beckers et al 2000b;Watabe-Rudolph et al 2002). Reduction of Tbx6 mRNA leads to altered abundance and distribution of mRNAs encoding the Notch pathway components Dll1, Dll3, Lfng, and Notch1 in the presomitic mesoderm, and to somite defects similar to mutations in Notch pathway components (Beckers et al 2000b).…”

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confidence: 93%

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WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos

Hofmann¹,

et al. 2004

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The subdivision of the paraxial mesoderm into somites, a metameric series of homologous subunits, is the most obvious sign of segmentation in early vertebrate embryos. During mouse embryogenesis, the first somites form in the posterior headfold region of the embryo around embryonic day 7.75 (E7.75). Subsequently, new somites condense at regular intervals in a strict anteriorto-posterior sequence from the unsegmented so-called presomitic mesoderm (psm) that lies caudally to the first somites. Somite condensation progresses while concomitantly new paraxial mesoderm cells are being generated caudally from the primitive streak and later from the tail bud elongating the embryo posteriorly.Somite formation is coupled to a molecular oscillator referred to as the segmentation clock, which has been revealed by the cyclic expression of genes in the psm. Expression of cyclic genes is periodic such that one wave of expression passes through the psm during the formation of one somite (Palmeirim et al. 1997;Forsberg et al. 1998;Jiang et al. 2000;Jouve et al. 2000;Aulehla et al. 2003). The segmentation clock is closely linked to Notch and WNT signaling activity. Most genes displaying cyclic activity encode components of the Notch pathway (Palmeirim et al. 1997;Forsberg et al. 1998;Jiang et al. 2000;Jouve et al. 2000); one other cyclic gene encodes the WNT pathway component Axin2 (Aulehla et al. 2003). Altered Notch signaling disrupts somite formation and patterning in Xenopus, zebrafish, and mouse embryos (Conlon et al. 1995;Hrabe de Angelis et al. 1997;Jen et al. 1999;Holley et al. 2000;Jiang et al. 2000;Sawada et al. 2000). Furthermore, mutations in some Notch pathway components, which lead to defects in somitogenesis, also affect the expression of cyclic genes (del Barco Barrantes et al. 1999;Jiang et al. 2000;Jouve et al. 2000;Dunwoodie et al. 2002), indicating that Notch signaling is essential for generating cyclic gene expression. Cyclic Lfng gene expression was shown in chick and mouse embryos to be essential for Lfng function (Dale et al. 2003;Serth et al. 2003). Disruption of WNT/ ␤-catenin signaling also affects somitogenesis and cyclic expression of Notch pathway components, whereas cyclic Axin2 expression is maintained when Notch signaling is impaired (Aulehla et al. 2003;Aulehla and Herrmann 2004), suggesting that WNT acts upstream of Notch in the segmentation clock. However, the exact molecular interplay between the various components of these pathways is not fully understood.T-box transcription factors as well as FGF and WNT signaling are essential regulators of formation and differentiation or maintenance of paraxial mesoderm in mouse embryos. Mutations in T, Fgfr1, Wnt3a, and Tbx6 cause defects in formation and differentiation of paraxial mesoderm. Loss of T gene function leads to failure of axis development and arrested somite formation (Wilkinson et al. 1990; Herrmann 1995) most likely because of impaired migration of mesodermal cells through the primitive streak (Wilson et al. 1993). The loss of Wnt3a also ...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 93%

WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos

Hofmann¹,

et al. 2004

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“…Somite formation can be rescued in these mutants with a Tbx6 transgene that is expressed at the correct time and place, but at lower levels than those observed in heterozygous mutant embryos (White et al, 2003). Although somites form at the correct time in the rescued mutants, the rostrocaudal patterning of the somites is defective, ultimately resulting in the fusion of the rib and vertebra, a phenotype also seen in the rib-vertebrae (rv) mutant in which the promoter of the Tbx6 locus is disrupted (Watabe-Rudolph et al, 2002;White et al, 2003). Taken together, these results show that Tbx6 is necessary for both the specification and the patterning of newly forming somites in the mouse.…”

Section: T-box Genes Regulate Paraxial Mesoderm Developmentmentioning

confidence: 99%

T‐box genes in early embryogenesis

Showell

Binder

Conlon

2003

Developmental Dynamics

270

229

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“…A ubiquitinated Nacke et al, 2000). Positional cloning of the rv mutation revealed that it was a Tbx6 hypomorphic allele (Watabe-Rudolph et al, 2002;White et al, 2003), and analysis of the promoter region of the Dll1 gene revealed binding sites for both the LEF1 and TBX6 transcription factors (Galceran et al, 2004;Hofmann et al, 2004; …”

Section: Figmentioning

confidence: 99%

The long and short of it: Somite formation in mice

Gridley

2006

Developmental Dynamics

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A fundamental characteristic of the vertebrate body plan is its segmentation along the anterior-posterior axis. This segmental pattern is established during embryogenesis by the formation of somites, the transient epithelial blocks of cells that derive from the unsegmented presomitic mesoderm. Somite formation involves a molecular oscillator, termed the segmentation clock, in combination with gradients of signaling molecules such as fibroblast growth factor 8, WNT3A, and retinoic acid. Disruption of somitogenesis in humans can result in disorders such as spondylocostal dysostosis, which is characterized by vertebral malformations. This review summarizes recent findings concerning the role of Notch signaling in the segmentation clock, the complex regulatory network that governs somitogenesis, the genes that cause inherited spondylocostal dysostosis, and the mechanisms that regulate bilaterally symmetric somite formation. Developmental Dynamics 235:2330 -2336, 2006.

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The mouse rib-vertebrae mutation is a hypomorphic Tbx6 allele

Cited by 66 publications

References 31 publications

WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos

WNT signaling, in synergy with T/TBX6, controls Notch signaling by regulating Dll1 expression in the presomitic mesoderm of mouse embryos

T‐box genes in early embryogenesis

The long and short of it: Somite formation in mice

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