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C. Tickle - One of the best experts on this subject based on the ideXlab platform.
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The Hox Gene Network in Vertebrate Limb Development
HOX Gene Expression, 2020Co-Authors: C. TickleAbstract:The Hox gene network has multiple roles in vertebrate Limb Development. One of its main functions is to encode positional information thus providing a “Hox” code for the pattern of structures along the long axis of the Limb. Another function of Hox genes that has emerged recently is to regulate expression of the Sonic hedgehog gene (Shh) which controls patterning of distal structures. Hox genes also play a major role in Development of the digits. The most recent advances have been the identification of control regions that drive Hox gene expression in the Limb.
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Limb Development: an international model for vertebrate pattern formation.
The International Journal of Developmental Biology, 2020Co-Authors: C. TickleAbstract:Limb Development is an excellent model for studying how patterns of differentiated cells and tissues are generated in vertebrate embryos. The cell interactions that mediate patterning have been discovered and, more recently, some of the molecules involved in these interactions have been identified. This has provided a direct link to genetics and thus to genes that cause human congenital Limb defects.
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The expression of Flrt3 during chick Limb Development
The International Journal of Developmental Biology, 2020Co-Authors: Terence Gordon Smith, C. TickleAbstract:The Flrt3 (Fibronectin-Leucine-Rich Transmembrane protein) gene encodes a fibronectin and leucine-rich repeat transmembrane protein whose expression is controlled by fibroblast growth factors (FGFs). FLRT3 has been implicated in neurite outgrowth after nerve damage, as a positive regulator of FGF signalling and in homotypic cell adhesion. Here we describe Flrt3 expression during chick embryonic Limb Development using whole-mount in situ hybridization. We found very dynamic expression during apical ridge formation and Limb bud outgrowth. Initially Flrt3 is expressed in the apical ectodermal ridge and underlying mesenchyme, but then becomes restricted to the dorsal and ventral sides of the apical ridge as a twin stripe. At later stages, abundant expression is seen in the hindLimb and in both the pectoral and pelvic girdle-forming regions. FLRT3 may have a crucial role in regulating cellular adhesion between the epithelial apical ridge and the underlying mesenchyme and in establishing the dorso-ventral position of the ridge.
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vertebrate Limb Development
Brenner's Encyclopedia of Genetics (Second Edition), 2013Co-Authors: C. TickleAbstract:The vertebrate Limb is a complex organ with precisely ordered arrays of differentiated cells and tissues making up skeleton, muscles, tendons, and ligaments. Its Development is an excellent model for pattern formation in addition to being an important process in its own right. Correct Development depends on three sets of cell–cell interactions that operate along each of the three axes of the Limb – proximo-distal, antero-posterior, and dorso-ventral. This article describes these interactions and the main molecules that mediate them. The discovery of the molecular basis of Limb Development and the genes involved has provided direct links with clinical genetics and human Limb malformations and also provides new perspectives on vertebrate Limb evolution and diversity.
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The contribution of chicken embryology to the understanding of vertebrate Limb Development
Mechanisms of Development, 2004Co-Authors: C. TickleAbstract:Abstract The chicken is an excellent model organism for studying vertebrate Limb Development, mainly because of the ease of manipulating the developing Limb in vivo. Classical chicken embryology has provided fate maps and elucidated the cell–cell interactions that specify Limb pattern. The first defined chemical that can mimic one of these interactions was discovered by experiments on developing chick Limbs and, over the last 15 years or so, the role of an increasing number of Developmentally important genes has been uncovered. The principles that underlie Limb Development in chickens are applicable to other vertebrates and there are growing links with clinical genetics. The sequence of the chicken genome, together with other recently assembled chicken genomic resources, will present new opportunities for exploiting the ease of manipulating the Limb.
Florian Witzmann - One of the best experts on this subject based on the ideXlab platform.
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deep time evolution of regeneration and preaxial polarity in tetrapod Limb Development
Nature, 2015Co-Authors: Nadia B. Fröbisch, Constanze Bickelmann, Jennifer C Olori, Florian WitzmannAbstract:Salamanders are the only tetrapod that can fully regenerate their Limbs and tail, a capacity that might be linked to their unique preaxial mode of Limb Development; here, data from fossils reveal the existence of preaxial polarity in various amphibians from the Carboniferous and Permian periods, suggesting that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes. Salamanders are unique among tetrapods in that they can fully regenerate their Limbs and tail, a capacity that might be linked to their unique preaxial mode of Limb Development, in which the first and second digits tend to develop before the others. Nadia Frobisch and colleagues demonstrate the existence of preaxial polarity in various amphibians from the Carboniferous and Permian periods. Limb regeneration has also been reported in one of these forms, demonstrating that both features were present together in amphibians 290 million years ago. These findings suggest that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes. Salamanders are the only modern tetrapods that retained regenerative capacities and preaxial polarity in Limb Development. Among extant tetrapods, salamanders are unique in showing a reversed preaxial polarity in patterning of the skeletal elements of the Limbs, and in displaying the highest capacity for regeneration, including full Limb and tail regeneration. These features are particularly striking as tetrapod Limb Development has otherwise been shown to be a highly conserved process1,2. It remains elusive whether the capacity to regenerate Limbs in salamanders is mechanistically and evolutionarily linked to the aberrant pattern of Limb Development; both are features classically regarded as unique to urodeles3. New molecular data suggest that salamander-specific orphan genes play a central role in Limb regeneration and may also be involved in the preaxial patterning during Limb Development4,5. Here we show that preaxial polarity in Limb Development was present in various groups of temnospondyl amphibians of the Carboniferous and Permian periods, including the dissorophoids Apateon and Micromelerpeton, as well as the stereospondylomorph Sclerocephalus. Limb regeneration has also been reported in Micromelerpeton6, demonstrating that both features were already present together in antecedents of modern salamanders 290 million years ago. Furthermore, data from lepospondyl ‘microsaurs’ on the amniote stem indicate that these taxa may have shown some capacity for Limb regeneration and were capable of tail regeneration7, including re-patterning of the caudal vertebral column that is otherwise only seen in salamander tail regeneration. The data from fossils suggest that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes. Salamanders are the only modern tetrapods that retained regenerative capacities as well as preaxial polarity in Limb Development.
Lee Niswander - One of the best experts on this subject based on the ideXlab platform.
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gli3 and plzf cooperate in proximal Limb patterning at early stages of Limb Development
Nature, 2005Co-Authors: Maria Barna, Pier Paolo Pandolfi, Lee NiswanderAbstract:The vertebrate Limb initially develops as a bud of mesenchymal cells that subsequently aggregate in a proximal to distal (P–D) sequence to give rise to cartilage condensations that prefigure all Limb skeletal components1. Of the three cardinal Limb axes, the mechanisms that lead to establishment and patterning of skeletal elements along the P–D axis are the least understood. Here we identify a genetic interaction between Gli3 (GLI-Kruppel family member 3) and Plzf (promyelocytic leukaemia zinc finger, also known as Zbtb16 and Zfp145), which is required specifically at very early stages of Limb Development for all proximal cartilage condensations in the hindLimb (femur, tibia, fibula). Notably, distal condensations comprising the foot are relatively unperturbed in Gli3-/-;Plzf-/- mouse embryos. We demonstrate that the cooperative activity of Gli3 and Plzf establishes the correct temporal and spatial distribution of chondrocyte progenitors in the proximal Limb-bud independently of known P–D patterning markers and overall Limb-bud size. Moreover, the Limb defects in Gli3-/-;Plzf-/- embryos correlate with the transient death of a specific subset of proximal mesenchymal cells that express bone morphogenetic protein receptor, type 1B (Bmpr1b) at the onset of Limb Development. These findings suggest that the Development of proximal and distal skeletal elements is distinctly regulated early during Limb-bud formation. The initial division of the vertebrate Limb into two distinct molecular domains is consistent with fossil evidence indicating that the upper and lower extremities of the Limb have different evolutionary origins2.
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eLS - Vertebrate Embryo: Limb Development
Encyclopedia of Life Sciences, 2003Co-Authors: Lee NiswanderAbstract:Limb Development in the vertebrate embryo is an excellent model system for the study of embryonic growth and pattern formation. This process is mediated through a wide range of cellular and molecular signals. Keywords: Limb; patterning; apical ectodermal ridge; zone of polarizing activity; dorsoventral
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Limb mutants: what can they tell us about normal Limb Development?
Current Opinion in Genetics & Development, 1997Co-Authors: Lee NiswanderAbstract:Abstract Classical mutations and those that derive from gene targeting have provided an important resource to explore the molecular control of vertebrate Limb Development. Recent studies have combined molecular analysis of Limb mutants with embryological approaches to understand the regulation of Limb patterning and growth.
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Function of FGF‐4 in Limb Development
Molecular Reproduction and Development, 1994Co-Authors: Lee Niswander, C. Tickle, Astrid Vogel, Gail R MartinAbstract:The apical ectodermal ridge plays a central role in Limb Development through its interactions with the underlying mesenchyme. Removal of the AER results in cessation of Limb outgrowth and leads to truncation of the Limb along the proximo-distal axis. The many functions attributed to the ridge include maintenance of the progress zone mesenchyme. Here, cells are stimulated to proliferate, are maintained in an undifferentiated state, and are assigned progressively more distal positional values as the Limb grows. The AER also functions to maintain the activity of the polarizing region, a region of mesenchyme which is thought to provide the primary signal for patterning along the antero-posterior axis
Nadia B. Fröbisch - One of the best experts on this subject based on the ideXlab platform.
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deep time evolution of regeneration and preaxial polarity in tetrapod Limb Development
Nature, 2015Co-Authors: Nadia B. Fröbisch, Constanze Bickelmann, Jennifer C Olori, Florian WitzmannAbstract:Salamanders are the only tetrapod that can fully regenerate their Limbs and tail, a capacity that might be linked to their unique preaxial mode of Limb Development; here, data from fossils reveal the existence of preaxial polarity in various amphibians from the Carboniferous and Permian periods, suggesting that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes. Salamanders are unique among tetrapods in that they can fully regenerate their Limbs and tail, a capacity that might be linked to their unique preaxial mode of Limb Development, in which the first and second digits tend to develop before the others. Nadia Frobisch and colleagues demonstrate the existence of preaxial polarity in various amphibians from the Carboniferous and Permian periods. Limb regeneration has also been reported in one of these forms, demonstrating that both features were present together in amphibians 290 million years ago. These findings suggest that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes. Salamanders are the only modern tetrapods that retained regenerative capacities and preaxial polarity in Limb Development. Among extant tetrapods, salamanders are unique in showing a reversed preaxial polarity in patterning of the skeletal elements of the Limbs, and in displaying the highest capacity for regeneration, including full Limb and tail regeneration. These features are particularly striking as tetrapod Limb Development has otherwise been shown to be a highly conserved process1,2. It remains elusive whether the capacity to regenerate Limbs in salamanders is mechanistically and evolutionarily linked to the aberrant pattern of Limb Development; both are features classically regarded as unique to urodeles3. New molecular data suggest that salamander-specific orphan genes play a central role in Limb regeneration and may also be involved in the preaxial patterning during Limb Development4,5. Here we show that preaxial polarity in Limb Development was present in various groups of temnospondyl amphibians of the Carboniferous and Permian periods, including the dissorophoids Apateon and Micromelerpeton, as well as the stereospondylomorph Sclerocephalus. Limb regeneration has also been reported in Micromelerpeton6, demonstrating that both features were already present together in antecedents of modern salamanders 290 million years ago. Furthermore, data from lepospondyl ‘microsaurs’ on the amniote stem indicate that these taxa may have shown some capacity for Limb regeneration and were capable of tail regeneration7, including re-patterning of the caudal vertebral column that is otherwise only seen in salamander tail regeneration. The data from fossils suggest that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes. Salamanders are the only modern tetrapods that retained regenerative capacities as well as preaxial polarity in Limb Development.
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Salamander Limb Development: Integrating genes, morphology, and fossils
Developmental Dynamics, 2011Co-Authors: Nadia B. Fröbisch, Neil H. ShubinAbstract:The Development of the tetrapod Limb during skeletogenesis follows a highly conservative pattern characterized by a general proximo-distal progression in the establishment of skeletal elements and a postaxial polarity in digit Development. Salamanders represent the only exception to this pattern and display an early establishment of distal autopodial structures, specifically the basale commune, an amalgamation of distal carpal and tarsal 1 and 2, and a distinct preaxial polarity in digit Development. This deviance from the conserved tetrapod pattern has resulted in a number of hypotheses to explain its Developmental basis and evolutionary history. Here we summarize the current knowledge of salamander Limb Development under consideration of the fossil record to provide a deep time perspective of this evolutionary pathway and highlight what data will be needed in the future to gain a better understanding of salamander Limb Development specifically and tetrapod Limb Development and evolution more broadly. Developmental Dynamics 240:1087–1099, 2011. V C 2011 Wiley-Liss, Inc.
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Limb ossification in the Paleozoic branchiosaurid Apateon (Temnospondyli) and the early evolution of preaxial dominance in tetrapod Limb Development.
Evolution & Development, 2007Co-Authors: Nadia B. Fröbisch, Robert L. Carroll, Rainer R. SchochAbstract:SUMMARY Despite the wide range of shapes and sizes that accompany a vast variety of functions, the Development of tetrapod Limbs follows a conservative pattern of de novo condensation, branching, and segmentation. Development of the zeugopodium and digital arch typically occurs in a posterior to anterior sequence, referred to as postaxial dominance, with a digital sequence of 4–3–5–2–1. The only exception to this pattern in all of living Tetrapoda can be found in salamanders, which display a preaxial dominance in Limb Development, a de novo condensation of a basale commune (distal carpal/tarsal 1+2) and a precoccial Development of digits I and II. These divergent patterns have puzzled researchers for over a century leading to various explanatory hypotheses. Despite many advances in research on tetrapod Limb Development, the divergent evolution of these two pathways and its causes are still not understood. Based on an extensive ontogenetic series we investigated the pattern of Limb Development of the 300 Ma old branchiosaurid amphibian Apateon. This revealed a preaxial dominance in Limb Development that was previously believed to be unique and derived for modern salamanders. The Branchiosauridae are favored as close relatives of extant salamanders in most phylogenetic hypotheses of the highly controversial origins and relationships of extant amphibians. The findings provide new insights into the evolution of Developmental pathways in tetrapod Limb Development, the relationships of modern amphibians with possible Paleozoic antecedents, and their initial timing of divergence.
Gail R Martin - One of the best experts on this subject based on the ideXlab platform.
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functions of fgf signalling from the apical ectodermal ridge in Limb Development
Nature, 2002Co-Authors: Francesca V Mariani, Gail R MartinAbstract:To determine the role of fibroblast growth factor (FGF) signalling from the apical ectodermal ridge (AER), we inactivated Fgf4 and Fgf8 in AER cells or their precursors at different stages of mouse Limb Development. We show that FGF4 and FGF8 regulate cell number in the nascent Limb bud and are required for survival of cells located far from the AER. On the basis of the skeletal phenotypes observed, we conclude that these functions are essential to ensure that sufficient progenitor cells are available to form the normal complement of skeletal elements, and perhaps other Limb tissues. In the complete absence of both FGF4 and FGF8 activities, Limb Development fails. We present a model to explain how the mutant phenotypes arise from FGF-mediated effects on Limb bud size and cell survival.
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fgf8 signalling from the aer is essential for normal Limb Development
Nature Genetics, 2000Co-Authors: Mark Lewandoski, Gail R MartinAbstract:Vertebrate Limb Development depends on signals from the apical ectodermal ridge (AER), which rims the distal tip of the Limb bud1. Removal of the AER in chick results in Limbs lacking distal skeletal elements2,3. Fibroblast growth factor (FGF) proteins can substitute for the AER (refs 4–7), suggesting that FGF signalling mediates AER activity. Of the four mouse Fgf genes (Fgf4 , Fgf8, Fgf9, Fgf17) known to display AER-specific expression domains within the Limb bud (AER-Fgfs), only Fgf8 is expressed throughout the AER. Moreover, Fgf8 expression precedes that of other AER-Fgfs (refs 8–13), suggesting that Fgf8 may perform unique functions early in Limb Development6,7. In mice, loss of function of Fgf4 (refs 13,14), Fgf9 (D. Ornitz, pers. comm.) or Fgf17 (ref. 15) has no effect on Limb formation. We report here that inactivating Fgf8 in early Limb ectoderm causes a substantial reduction in Limb-bud size, a delay in Shh expression, misregulation of Fgf4 expression, and hypoplasia or aplasia of specific skeletal elements. Our data identify Fgf8 as the only known AER-Fgf individually necessary for normal Limb Development, and provide insight into the function of Fgf signalling from the AER in the normal outgrowth and patterning of the Limb.
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Function of FGF‐4 in Limb Development
Molecular Reproduction and Development, 1994Co-Authors: Lee Niswander, C. Tickle, Astrid Vogel, Gail R MartinAbstract:The apical ectodermal ridge plays a central role in Limb Development through its interactions with the underlying mesenchyme. Removal of the AER results in cessation of Limb outgrowth and leads to truncation of the Limb along the proximo-distal axis. The many functions attributed to the ridge include maintenance of the progress zone mesenchyme. Here, cells are stimulated to proliferate, are maintained in an undifferentiated state, and are assigned progressively more distal positional values as the Limb grows. The AER also functions to maintain the activity of the polarizing region, a region of mesenchyme which is thought to provide the primary signal for patterning along the antero-posterior axis