Vertebrate limb bud development: moving towards integrative analysis of organogenesis

Zeller, Rolf; López-Rı́os, Javier; Zúñiga, Aimée

doi:10.1038/nrg2681

Cited by 406 publications

(434 citation statements)

References 106 publications

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“…At precondensation stages, distal limb bud mesenchyme expresses both Fgfr1 and Fgfr2 (Orr-Urtreger et al 1991;Sheeba et al 2010), whereas Fgfr3 and Fgfr4 are not detected in undifferentiated distal limb bud mesenchyme (Sheeba et al 2010). Distal limb bud FGFRs respond to FGFs produced by the apical ectodermal ridge (AER) of the limb bud (Zeller et al 2009). AER FGFs (primarily FGF4 and FGF8) signal to limb mesenchyme and are required for proximo-distal outgrowth of the limb bud.…”

Section: Fgf Signaling During Skeletal Developmentmentioning

confidence: 99%

Fibroblast growth factor signaling in skeletal development and disease

2015

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Fibroblast growth factor (FGF) signaling pathways are essential regulators of vertebrate skeletal development. FGF signaling regulates development of the limb bud and formation of the mesenchymal condensation and has key roles in regulating chondrogenesis, osteogenesis, and bone and mineral homeostasis. This review updates our review on FGFs in skeletal development published in Genes & Development in 2002, examines progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis, and explores the mechanisms by which mutations in FGF signaling molecules cause skeletal malformations in humans. Links between FGF signaling pathways and other interacting pathways that are critical for skeletal development and could be exploited to treat genetic diseases and repair bone are also explored.

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Section: Fgf Signaling During Skeletal Developmentmentioning

confidence: 99%

Fibroblast growth factor signaling in skeletal development and disease

2015

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“…Together, the AER and ZPA coordinate gradients of growth factors to regulate formation, size, shape, and location of future bone and joints in the appendicular skeleton (reviewed in Johnson and Tabin 1997;Galloway and Tabin 2008). Interlinked feedback loops between AER, ZPA, and mesenchymal BMP signaling regulate initiation, propagation, and termination of the limb signaling system (reviewed in Benazet et al 2009;Zeller et al 2009). Disruption of these feedback loops result in impaired progression of limb bud development and specification of digit identity (Kawakami et al 1996;Ahn et al 2001;Khokha et al 2003;Ovchinnikov et al 2006;Montero et al 2008;Suzuki et al 2008;Benazet et al 2009).…”

Section: Roles Of Tgf-b and Bmp Signaling In Limb Formation And Digitmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

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The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

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“…These CNEs participate in gene regulatory networks for axial formation, outgrowth, and chondrogenic differentiation in limb development (Zeller et al 2009). We found apparent sequence similarity in CNEs for the limb enhancer of bmp7 (Adams et al 2007) and the limb enhancer (CNE11) of gli3 (Abbasi et al 2010) between tetrapods and coelacanth, whereas such similarities were not observed in the corresponding genomic regions of ray-finned fishes (Fig.…”

Section: Genes For Limb Developmentmentioning

confidence: 99%

Coelacanth genomes reveal signatures for evolutionary transition from water to land

et al. 2013

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Coelacanths are known as ''living fossils,'' as they show remarkable morphological resemblance to the fossil record and belong to the most primitive lineage of living Sarcopterygii (lobe-finned fishes and tetrapods). Coelacanths may be key to elucidating the tempo and mode of evolution from fish to tetrapods. Here, we report the genome sequences of five coelacanths, including four Latimeria chalumnae individuals (three specimens from Tanzania and one from Comoros) and one L. menadoensis individual from Indonesia. These sequences cover two African breeding populations and two known extant coelacanth species. The genome is~2.74 Gbp and contains a high proportion (~60%) of repetitive elements. The genetic diversity among the individuals was extremely low, suggesting a small population size and/or a slow rate of evolution. We found a substantial number of genes that encode olfactory and pheromone receptors with features characteristic of tetrapod receptors for the detection of airborne ligands. We also found that limb enhancers of bmp7 and gli3, both of which are essential for limb formation, are conserved between coelacanth and tetrapods, but not ray-finned fishes. We expect that some tetrapod-like genes may have existed early in the evolution of primitive Sarcopterygii and were later co-opted to adapt to terrestrial environments. These coelacanth genomes will provide a cornerstone for studies to elucidate how ancestral aquatic vertebrates evolved into terrestrial animals.

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Vertebrate limb bud development: moving towards integrative analysis of organogenesis

Cited by 406 publications

References 106 publications

Fibroblast growth factor signaling in skeletal development and disease

Fibroblast growth factor signaling in skeletal development and disease

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

Coelacanth genomes reveal signatures for evolutionary transition from water to land

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