Heterochronic differences of Hoxa-11 expression in Xenopus fore- and hind limb development: Evidence for lower limb identity of the anuran ankle bones

Profile data on normal lower limb development and specifically tibiofemoral angle development in black, Setswana-speaking South African children are lacking. This study aimed to provide profiles on the development of the tibiofemoral angle, hip anteversion angle and tibial torsion angles in two- to nine-year-old children. Measurements of the tibiofemoral angle, intercondylar distances or intermalleolar distances, quadriceps-angle, hip anteversion- and tibial torsion angle were clinically obtained from 691 healthy two- to nine-year-old children. Two-year-old children presented with closest to genu varum at −3.4° (±3.4°). At three years, a peak of −5.7° (±2.3°) genu valgum was seen, which plateaued at −4.5° (±2.1°) at age nine years. Intermalleolar distance results support tibiofemoral angle observations. Small quadricep-angles were observed in the two-year-old group, (−3.81° ± 3.77°), which increased to a mean peak of −9.2° (±4.4°) in nine-year-olds. From the age of four years old, children presented with neutral tibial torsion angles, whilst two- and three-year-olds presented with internal tibial torsion angles. Anteversion angles were the greatest in three-year-olds at 77.6° ± 13.8° and decreased to a mean angle of 70.8° ± 6.9° in nine-year-olds. The tibiofemoral angle developed similarly to those tested in European, Asian and Nigerian children, but anteversion- and internal tibial torsion angles were greater in the Setswana population than angles reported in European children. Our findings indicate that lower limb development differs in different environments and traditions of back-carrying may influence the development, which requires further investigation.

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Kugelzellen in larval anuran epidermis: an ultrastructural study on tadpoles of Pelobates cultripes (Pelobatidae) and Phyllobates bicolor (Dendrobatidae)

Contributions to Zoology ◽

10.1163/18759866-07604001 ◽

2007 ◽

Vol 76 (4) ◽

pp. 213-220 ◽

Cited By ~ 2

Author(s):

Giovanni Delfino ◽

Sara Quagliata ◽

Filippo Giachi ◽

Cecilia Malentacchi

Keyword(s):

Cell Surface ◽

Ultrastructural Study ◽

Limb Development ◽

Leydig Cells ◽

Hind Limb ◽

Three Dimensional ◽

Basal Layer ◽

Dimensional Network ◽

Clawed Frog ◽

Pelobates Cultripes

Prior to hind limb development, tadpoles of the western spadefoot frog Pelobates cultripes (Pelobatidae) and dart-arrow frog Phyllobates bicolor (Dendrobatidae) possess large clear cells in the basal layer of the epidermis. These cells closely resemble Kugelzellen (KZn) of larval clawed frog, Xenopus laevis (Pipidae) and share ultrastructural traits with Leydig cells (LCs) of Caudata and Caecilia. In both species, KZn possess a transparent cytoplasm and a remarkable peripheral cytoskeleton of tonofilaments: in the arrow frog tonofilaments form bands parallel to the cell surface, in the spadefoot frog thin bundles, arranged in a three-dimensional network. KZn combine turgor (resulting from the hydrated cytoplasm) with stiffness (from peripheral cytoskeleton), thus providing structural stability to the larval epidermis.

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Missing Midline Metatarsals Conform to Plantar Arterial Arch Dysgenesis

Journal of the American Podiatric Medical Association ◽

10.7547/18-031 ◽

2020 ◽

Vol 110 (3) ◽

Cited By ~ 1

Author(s):

David R. Hootnick

Keyword(s):

Risk Factor ◽

Lower Extremity ◽

Lower Limb ◽

Limb Development ◽

Long Bone ◽

Long Bones ◽

Adult Pattern ◽

Embryonic Limb ◽

A Current ◽

Embryonic Vessels

Midline metatarsal ray deficiencies, which occur in approximately half of congenital short limbs with fibular deficiency, provide the most distal and compelling manifestation of a fluid spectrum of human lower-extremity congenital long bone reductions; this spectrum syndromically affects the long bone triad of the proximal femur, fibula, and midline metatarsals. The bony deficiencies correspond to sites of rapid embryonic arterial transitioning. Long bones first begin to ossify because of vascular invasions of their respective mesenchymal/cartilage anlagen, proceeding in a proximal-to-distal sequence along the forming embryonic limb. A single-axis artery forms initially in the embryonic lower limb by means of vasculogenesis. Additional arteries evolve in overlapping transitional waves, in proximity to the various anlagen, during the sixth and seventh weeks after fertilization. An adult pattern of vessels presents by the eighth week. Arterial alterations, in the form of retained primitive embryonic vessels and/or reduced absent adult vessels, have been observed clinically at the aforementioned locations where skeletal reductions occur. Persistence of primitive vessels in association with the triad of long bone reductions allows a heuristic estimation of the time, place, and nature of such coupled vascular and bony dysgeneses. Arterial dysgenesis is postulated to have occurred when the developing arterial and skeletal structures were concurrently vulnerable to teratogenic insults because of embryonic arterial instability, a risk factor during arterial transition. It is herein hypothesized that flawed arterial transitions subject the prefigured long bone cartilage models of the rapidly growing limb to the risk of teratogenesis at one or more of the then most rapidly growing sites. Midline metatarsal deficiency forms the keystone of this developmental concept of an error of limb development, which occurs as a consequence of failed completion of the medial portion of the plantar arch. Therefore, the historical nomenclature of congenital long bone deficiencies will benefit from modification from a current reliance on empirical physical taxonomies to a developmental foundation.

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A steady efflux of ionic current predicts hind limb development in the axolotl

Journal of Experimental Zoology ◽

10.1002/jez.1402280309 ◽

1983 ◽

Vol 228 (3) ◽

pp. 491-503 ◽

Cited By ~ 32

Author(s):

Richard B. Borgens ◽

Marie F. Rouleau ◽

Louis E. DeLanney

Keyword(s):

Limb Development ◽

Hind Limb ◽

Ionic Current

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Realization of a prosthesis of the lower limb: Development of kinematics

Robotics and Computer-Integrated Manufacturing ◽

10.1016/0736-5845(91)90012-h ◽

1991 ◽

Vol 8 (3) ◽

pp. 137-142 ◽

Cited By ~ 2

Author(s):

Alberto Rovetta ◽

Xia Wen ◽

Francesca Cosmi

Keyword(s):

Lower Limb ◽

Limb Development

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Effects of laboratory ultraviolet radiation and natural sunlight on survival and development of Rana pipiens

Canadian Journal of Zoology ◽

10.1139/z00-040 ◽

2000 ◽

Vol 78 (6) ◽

pp. 1092-1100 ◽

Cited By ~ 16

Author(s):

Gerald T Ankley ◽

Joseph E Tietge ◽

Gary W Holcombe ◽

David L DeFoe ◽

Stephen A Diamond ◽

...

Keyword(s):

Uv Radiation ◽

Limb Development ◽

Hind Limb ◽

Rana Pipiens ◽

Life Stage ◽

Leopard Frog ◽

Natural Sunlight ◽

Survival And Development ◽

Full Intensity ◽

Environ Toxicol

Changes in solar ultraviolet (UV) radiation have been proposed as a possible factor contributing to seeming increases in hind-limb malformations in anuran amphibians in North America. One purpose of this study was to reproduce results from an earlier experiment (G.T. Ankley, J.E. Tietge, D.L. DeFoe, K.M. Jensen, G.W. Holcombe, E.J. Durhan, and S.A. Diamond. 1998. Environ. Toxicol. Chem. 17: 25302542) in which Rana pipiens (northern leopard frog) developed hind-limb ectromelia and ectrodactyly when exposed to an artificial source of UV radiation in the laboratory. Additionally, we sought to assess the effects of natural sunlight on survival and development in this species. Animals exposed to UV radiation in the laboratory from stage 2526 (just prior to hind-limb development) through forelimb emergence exhibited a dose-dependent elevation of hind-limb dysmorphogenesis. The observed malformations usually were bilateral and typically symmetrical, and consisted primarily of missing and reduced digits. Exposure of animals at this life stage to full intensity natural sunlight caused significant mortality, while exposure to screened sunlight (ca. 5060% of ambient) resulted in an elevated incidence of abnormal hind limb pathology (ectromelia, ectrodactyly) identical to that observed in organisms exposed to UV radiation in the laboratory. Owing to uncertainties in dose extrapolation, for example, in the context of animal behavior, the potential significance of our results in terms of explaining adverse effects in amphibians from the field is as yet unclear.

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Extent of Duplication in Lower-Limb Malformations Suggests the Time of the Teratogenic Insult

PEDIATRICS ◽

10.1542/peds.91.2.411 ◽

1993 ◽

Vol 91 (2) ◽

pp. 411-413

Author(s):

David S. Packard ◽

E. Mark Levinsohn ◽

David R. Hootnick

Keyword(s):

Lower Limb ◽

Limb Development ◽

Lower Limbs ◽

Relative Time ◽

Vertebrate Limb ◽

The Future ◽

Vertebrate Limb Development ◽

Limb Malformations ◽

Human Limb ◽

Limb Specification

Investigations of vertebrate limb development have suggested that a process called "specification" instructs the cells of the future limb as to which tissues they should form. This process proceeds in a wave-like manner, starting at the most proximal levels of the future limb and ending at its distal tip. Human limb specification probably occurs during the fourth and fifth weeks of development. It is proposed that human limb duplications result from errors of specification and, furthermore, that the more distal the duplication, the later the occurrence of the teratogenic event during the specification process. Therefore, among human lower limbs with duplications, one may be able to estimate the relative time of the teratogenic event by comparing the levels at which the duplications occur.

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Pigeon foot feathering reveals conserved limb identity networks

10.1101/602987 ◽

2019 ◽

Author(s):

Elena F. Boer ◽

Hannah F. Van Hollebeke ◽

Sungdae Park ◽

Carlos R. Infante ◽

Douglas B. Menke ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Limb Development ◽

Limb Bud ◽

Differentially Expressed ◽

Evolutionarily Conserved ◽

Genes Encoding ◽

Embryonic Limb ◽

Summary Statement ◽

Limb Identity

AbstractThe tetrapod limb is a stunning example of evolutionary diversity, with dramatic variation not only among distantly related species, but also between the serially homologous forelimbs (FLs) and hindlimbs (HLs) within species. Despite this variation, highly conserved genetic and developmental programs underlie limb development and identity in all tetrapods, raising the question of how limb diversification is generated from a conserved toolkit. In some breeds of domestic pigeon, shifts in the expression of two conserved limb identity transcription factors,PITX1andTBX5, are associated with the formation of feathered HLs with partial FL identity. To determine how modulation ofPITX1andTBX5expression affects downstream gene expression, we compared the transcriptomes of embryonic limb buds from pigeons with scaled and feathered HLs. We identified a set of differentially expressed genes enriched for genes encoding transcription factors, extracellular matrix proteins, and components of developmental signaling pathways with important roles in limb development. A subset of the genes that distinguish scaled and feathered HLs are also differentially expressed between FL and scaled HL buds in pigeons, pinpointing a set of gene expression changes downstream ofPITX1andTBX5in the partial transformation from HL to FL identity. We extended our analyses by comparing pigeon limb bud transcriptomes to chicken, anole lizard, and mammalian datasets to identify deeply conservedPITX1- andTBX5-regulated components of the limb identity program. Our analyses reveal a suite of predominantly low-level gene expression changes that are conserved across amniotes to regulate the identity of morphologically distinct limbs.Summary statementIn feather-footed pigeons, mutant alleles ofPITX1andTBX5drive the partial redeployment of an evolutionarily conserved forelimb genetic program in the hindlimb.

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Inhibition of eNOS by L-NAME resulting in rat hind limb developmental defects through PFKFB3 mediated angiogenetic pathway

Scientific Reports ◽

10.1038/s41598-020-74011-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ziqiang Wu ◽

Huan Yao ◽

Huan Xu ◽

Yang Wang ◽

Wangming Hu ◽

...

Keyword(s):

Extracellular Matrix ◽

Endothelial Cells ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Limb Development ◽

Hind Limb ◽

Critical Role ◽

Muscle Cells ◽

Developmental Defects ◽

Pregnant Rat

Abstract l-arginine/NOS/NO signaling pathway plays a critical role in controlling variety of vascular diseases. However, whether NOS inhibition by L-NAME suppresses late embryonic development is undefined. The aim of this study is to determine whether NOS inhibition by L-NAME is critical for late embryonic rat hind limb development. The pregnant rat at E13.5 administrated L-NAME by consecutive intraperitoneal injection. The embryos been harvested from E16.5 to E 20.5. Hematoxylin and Eosin Staining, Immunofluorescence and Immunohistochemistry performed to determine hind limb Vasculogenesis, HUVEC culture, Adenoviral PFKFB3 infection, Real time PCR and western blot were performed to determine whether l-arginine/NOS/NO pathway controlling late embryonic hind limb development through PFKFB3 mediated angiogenetic pathway. NOS inhibition by L-NAME resulting in late embryonic hind limb developmental defects characterized by severe hemorrhage. The in vivo studies showed that NOS inhibition strongly suppressed hind limb angiogenetic remodeling by impairing differentiation of endothelial cells and smooth muscle cells, and extracellular matrix synthesis. For underlie mechanism, our studies indicated that L-NAME treatment dramatically suppresses PFKFB3 expression in hematopoietic progenitor cells, tubulogenetic endothelial cells and smooth muscle cells. Knockdown of PFKFB3 dramatically inhibits the expression of angiogenetic genes, as well as tubulogenesis and extracellular matrix related genes. Taken together, our data in this study demonstrated that l-arginine-eNOS-NO pathway is important for rat hind limb development during late embryonic stage. This could be both a useful animal model and a promising therapeutic treatment for defects of late embryonic developmental hind limbs.

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Electron Microscopic Observations on the Basal Lamina of Chick Limb Buds After Trypsin and Edta Treatment

Journal of Cell Science ◽

10.1242/jcs.3.3.373 ◽

1968 ◽

Vol 3 (3) ◽

pp. 373-380

Author(s):

S. C. GOEL ◽

A. JURAND

Keyword(s):

Basal Lamina ◽

Salt Solution ◽

Limb Development ◽

Hind Limb ◽

Physiological Role ◽

Electron Microscopic ◽

Limb Buds ◽

Edta Treatment ◽

Subsequent Separation ◽

Calcium And Magnesium

Chick hind-limb buds were treated first with calcium- and magnesium-free balanced salt solution and then with either trypsin or EDTA. Treatment with these chemicals, and the subsequent separation of the ectodermal covering from the mesoderm, produces two different results as regards the basal lamina. In the case of trypsin, the lamina stays with the ectoderm but shows signs of probable tryptic digestion. After EDTA treatment the lamina stays with the mesoderm and becomes very loose and swollen. This loosening allows the structure of the otherwise compact lamina to be resolved so that banded collagen fibrils are seen participating in its substance. The above observations are discussed in relation to the mode of action of the two chemicals. The physiological role and the origin of the basal lamina, as well as the possible implications of the present findings to the question of limb development and morphogenesis, are also discussed. A note has also been made regarding the various terms used to describe the epitheliomesenchymal junction layers.

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