Regulation of limb bud initiation and limb‐type morphology

Duboc, Véronique; Logan, Malcolm

doi:10.1002/dvdy.22582

Cited by 92 publications

(88 citation statements)

References 87 publications

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“…Contrary to previous predictions, we observed normal expression of Pitx1 in Ctnnb1 cKO as compared with control embryos (Fig. 2G,H), suggesting that -catenin activity is unlikely to be required for the genetic program that drives limb type specificity (Duboc and Logan, 2011;Kawakami et al, 2003b;Logan, 2003).…”

Section: Research Articlecontrasting

confidence: 99%

“…The vertebrate limb has served as an ideal model system for understanding the mechanisms of organogenesis, including initiation, outgrowth, patterning and morphogenesis (Towers and Tickle, 2009;Zeller et al, 2009). It also provides a unique setting in which to study the development of the forelimb versus the hindlimb, which are two morphologically distinct but serially homologous organs (Duboc and Logan, 2011;Kawakami et al, 2003b;Logan, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice

et al. 2011

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SUMMARYThe transcriptional basis of vertebrate limb initiation, which is a well-studied system for the initiation of organogenesis, remains elusive. Specifically, involvement of the -catenin pathway in limb initiation, as well as its role in hindlimb-specific transcriptional regulation, are under debate. Here, we show that the -catenin pathway is active in the limb-forming area in mouse embryos. Furthermore, conditional inactivation of -catenin as well as Islet1, a hindlimb-specific factor, in the lateral plate mesoderm results in a failure to induce hindlimb outgrowth. We further show that Islet1 is required for the nuclear accumulation of -catenin and hence for activation of the -catenin pathway, and that the -catenin pathway maintains Islet1 expression. These two factors influence each other and function upstream of active proliferation of hindlimb progenitors in the lateral plate mesoderm and the expression of a common factor, Fgf10. Our data demonstrate that Islet1 and -catenin regulate outgrowth and Fgf10-Fgf8 feedback loop formation during vertebrate hindlimb initiation. Our study identifies Islet1 as a hindlimb-specific transcriptional regulator of initiation, and clarifies the controversy regarding the requirement of -catenin for limb initiation.

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Section: Research Articlecontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice

et al. 2011

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“…Fgf10 is expressed in limb bud mesenchyme and signals to the Fgfr2b receptor expressed in the AER to induce expression of Fgf8 there. By contrast, Fgfr2c is expressed in both the mesoderm and ectoderm of the developing limb bud (Lizarraga et al, 1999;Duboc and Logan, 2011). The detection of mRNAs from Fgf10 and Fgfr2c, but not Fgf8 or Fgfr2b in immortomouse-derived limb bud cell lines thus indicates their derivation from the limb mesenchyme (Fig.…”

Section: Image Analysismentioning

confidence: 92%

Anterior-posterior differences in HoxD chromatin topology in limb development

et al. 2012

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SUMMARYA late phase of HoxD activation is crucial for the patterning and growth of distal structures across the anterior-posterior (A-P) limb axis of mammals. Polycomb complexes and chromatin compaction have been shown to regulate Hox loci along the main body axis in embryonic development, but the extent to which they have a role in limb-specific HoxD expression, an evolutionary adaptation defined by the activity of distal enhancer elements that drive expression of 5Ј Hoxd genes, has yet to be fully elucidated. We reveal two levels of chromatin topology that differentiate distal limb A-P HoxD activity. Using both immortalised cell lines derived from posterior and anterior regions of distal E10.5 mouse limb buds, and analysis in E10.5 dissected limb buds themselves, we show that there is a loss of polycomb-catalysed H3K27me3 histone modification and a chromatin decompaction over HoxD in the distal posterior limb compared with anterior. Moreover, we show that the global control region (GCR) long-range enhancer spatially colocalises with the 5Ј HoxD genomic region specifically in the distal posterior limb. This is consistent with the formation of a chromatin loop between 5Ј HoxD and the GCR regulatory module at the time and place of distal limb bud development when the GCR participates in initiating Hoxd gene quantitative collinearity and Hoxd13 expression. This is the first example of A-P differences in chromatin compaction and chromatin looping in the development of the mammalian secondary body axis (limb).

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“…Thus, the primordial function of Tbx1/10 in chordates might have been branchial arch patterning and ventral somite specification, functions retained by the Tbx1 gene while Tbx10 lost its role in pharyngeal arch patterning and gained a novel role in hindbrain development. Another example is AmphiTbx4/5, which is the ortholog of vertebrate Tbx4 and Tbx5, which both have roles in limb development and, in addition, Tbx5 has a role in heart development (Duboc and Logan, 2011;Greulich et al, 2011). AmphiTbx4/5 is transiently expressed in restricted, bilateral areas of ventral mesoderm that superficially resemble the restricted, limb field-specific expression of Tbx4 and Tbx5 in vertebrates.…”

Section: Early Development Gastrulation and Somite Patterningmentioning

confidence: 99%

The T-box gene family: emerging roles in development, stem cells and cancer

2014

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The T-box family of transcription factors exhibits widespread involvement throughout development in all metazoans. T-box proteins are characterized by a DNA-binding motif known as the T-domain that binds DNA in a sequence-specific manner. In humans, mutations in many of the genes within the T-box family result in developmental syndromes, and there is increasing evidence to support a role for these factors in certain cancers. In addition, although early studies focused on the role of T-box factors in early embryogenesis, recent studies in mice have uncovered additional roles in unsuspected places, for example in adult stem cell populations. Here, I provide an overview of the key features of T-box transcription factors and highlight their roles and mechanisms of action during various stages of development and in stem/progenitor cell populations.

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Regulation of limb bud initiation and limb‐type morphology

Cited by 92 publications

References 87 publications

Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice

Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice

Anterior-posterior differences in HoxD chromatin topology in limb development

The T-box gene family: emerging roles in development, stem cells and cancer

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