Activator-to-Repressor Conversion of T-Box Transcription Factors by the Ripply Family of Groucho/TLE-Associated Mediators

Kawamura, Akinori; Koshida, Shinji; Takada, Shinji

doi:10.1128/mcb.01754-07

Cited by 62 publications

(69 citation statements)

References 38 publications

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“…The Bowline/ripply family proteins mediate interactions between Tbx6/ tbx24, which are transcriptional activators that are commonly required for somite segmentation program (Nikaido et al, 2002;Yasuhiko et al, 2006), and the transcriptional corepressors XGrg-4/Groucho Kawamura et al, 2008). At the end of somitogenesis, it is likely that this interaction results in the suppression of Tbx6/tbx24-dependent transcription of genes that are essential for the somite segmentation program.…”

Section: Identification and Characterization Of Novel Somitogenesis-rmentioning

confidence: 99%

In vitro organogenesis from undifferentiated cells in Xenopus

Asashima

Ito

Chan

et al. 2009

Developmental Dynamics

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Amphibians have been used for over a century as experimental animals. In the field of developmental biology in particular, much knowledge has been accumulated from studies on amphibians, mainly because they are easy to observe and handle. Xenopus laevis is one of the most intensely investigated amphibians in developmental biology at the molecular level. Thus, Xenopus is highly suitable for studies on the mechanisms of organ differentiation from not only a single fertilized egg, as in normal development, but also from undifferentiated cells, as in the case of in vitro organogenesis. Based on the established in vitro organogenesis methods, we have identified many genes that are indispensable for normal development in various organs. These experimental systems are useful for investigations of embryonic development and for advancing regenerative medicine. Developmental Dynamics 238:1309 -1320, 2009.

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Section: Identification and Characterization Of Novel Somitogenesis-rmentioning

confidence: 99%

In vitro organogenesis from undifferentiated cells in Xenopus

Asashima

Ito

Chan

et al. 2009

Developmental Dynamics

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“…5A). Moreover, the tetrapeptide FPVQ in the Ripply/BDLC region, which is essential for interactions with T-box proteins (Kawamura et al, 2008) was also completely conserved (Fig. 5A).…”

Section: Isolation and Characterization Of A Third Xenopus Bowline/ Rmentioning

confidence: 99%

“…We have previously shown that Bowline interacts with Tbx6 protein via the Ripply/BDLC domain and suppresses the transcriptional activity of Tbx6 . Similarly, in zebrafish, Ripply1 interacts with Tbx24, which is related to Tbx6, to suppress the transcriptional activity of Tbx24 (Kawamura et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

The Xenopus Bowline/Ripply family proteins negatively regulate the transcriptional activity of T-box transcription factors

et al. 2009

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Bowline, which is a member of the Xenopus Bowline/Ripply family of proteins, represses the transcription of somitogenesis-related genes before somite segmentation, which makes Bowline indispensable for somitogenesis. Although there are three bowline/Ripply family genes in each vertebrate species, it is not known whether the Bowline/Ripply family proteins share a common role in development. To elucidate their developmental roles, we examined the expression patterns and functions of the Xenopus Bowline/Ripply family proteins Bowline, Ledgerline, and a novel member of this protein family, xRipply3. We found that the expression patterns of bowline and ledgerline overlapped in the presomitic mesoderm (PSM), whereas ledgerline was additionally expressed in the newly formed somites. In addition, we isolated xRipply3, which is expressed in the pharyngeal region. Co-immunoprecipitation assays revealed that Ledgerline and xRipply3 interacted with T-box proteins and the transcriptional co-repressor Groucho/TLE. In luciferase assays, xRipply3 weakly suppressed the transcriptional activity of Tbx1, while Ledgerline strongly suppressed that of Tbx6. In line with the repressive role of Ledgerline, knockdown of Ledgerline resulted in enlargement of expression regions of the somitogenesis-related-genes mespb and Tbx6. Inhibition of histone deacetylase activity increased the expression of mespb, as seen in the Bowline and Ledgerline knockdown experiments. These results suggest that the Groucho-HDAC complex is required for the repressive activity of Bowline/Ripply family proteins during Xenopus somitogenesis. We conclude that although the Xenopus Bowline/Ripply family proteins Bowline, Ledgerline and xRipply3 are expressed differentially, they all act as negative regulators of T-box proteins.

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“…68,69 We identified a chromosome 6q14.2 microduplication involving RIPPLY2 that incompletely segregates with talipes equinovarus over three generations. Furthermore, the RIPPLY family of proteins have previously been shown to regulate T-box transcription factors during embryogenesis, 70 suggesting a possible link to the PITX1-TBX4 pathway during limb development.…”

Section: Copy Number Analysis In Talipes Equinovarusmentioning

confidence: 99%

Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development

et al. 2012

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Talipes equinovarus is one of the most common congenital musculoskeletal anomalies and has a worldwide incidence of 1 in 1000 births. A genetic predisposition to talipes equinovarus is evidenced by the high concordance rate in twin studies and the increased risk to first-degree relatives. Despite the frequency of isolated talipes equinovarus and the strong evidence of a genetic basis for the disorder, few causative genes have been identified. To identify rare and/or recurrent copy number variants, we performed a genome-wide screen for deletions and duplications in 413 isolated talipes equinovarus patients using the Affymetrix 6.0 array. Segregation analysis within families and gene expression in mouse E12.5 limb buds were used to determine the significance of copy number variants. We identified 74 rare, gene-containing copy number variants that were present in talipes equinovarus probands and not present in 759 controls or in the Database of Genomic Variants. The overall frequency of copy number variants was similar between talipes equinovarus patients compared with controls. Twelve rare copy number variants segregate with talipes equinovarus in multiplex pedigrees, and contain the developmentally expressed transcription factors and transcriptional regulators PITX1, TBX4, HOXC13, UTX, CHD (chromodomain protein)1, and RIPPLY2. Although our results do not support a major role for recurrent copy number variations in the etiology of isolated talipes equinovarus, they do suggest a role for genes involved in early embryonic patterning in some families that can now be tested with large-scale sequencing methods. INTRODUCTIONIsolated talipes equinovarus, also called clubfoot, is one of the most common serious congenital birth defects with an estimated birth prevalence of 1 per 1000 live births. 1 Talipes equinovarus consists of malalignment of the bones and joints of the foot and ankle, and is distinguished from positional foot anomalies because it is rigid and not passively correctable (Figure 1). Approximately 20% of talipes equinovarus cases are associated with chromosomal abnormalities, or known genetic syndromes 2,3 and it is a common component of several neurological disorders, including distal arthrogryposis, myotonic dystrophy, and myelomeningocele. Despite the frequency of talipes equinovarus in neurological disorders, no consistent neuromuscular abnormalities have been identified in isolated talipes equinovarus patients using muscle biopsy or electrophysiological examinations. [4][5][6][7] Most cases of clubfeet (80%) occur as isolated birth defects and are considered idiopathic. 8 Approximately 25% of patients with isolated talipes equinovarus report a family history of talipes equinovarus, suggesting a genetic basis for this disorder. 9 Twin studies also support a role for genetic factors, as identical twins have a 33% concordance rate for talipes

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Activator-to-Repressor Conversion of T-Box Transcription Factors by the Ripply Family of Groucho/TLE-Associated Mediators

Cited by 62 publications

References 38 publications

In vitro organogenesis from undifferentiated cells in Xenopus

In vitro organogenesis from undifferentiated cells in Xenopus

The Xenopus Bowline/Ripply family proteins negatively regulate the transcriptional activity of T-box transcription factors

Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development

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