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1.
Nature ; 626(8001): 1042-1048, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38418917

RESUMO

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'1-3, with a proposed role in contributing to human bipedalism4-6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene7-9-pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.


Assuntos
Processamento Alternativo , Evolução Molecular , Hominidae , Proteínas com Domínio T , Cauda , Animais , Humanos , Camundongos , Processamento Alternativo/genética , Elementos Alu/genética , Modelos Animais de Doenças , Genoma/genética , Hominidae/anatomia & histologia , Hominidae/genética , Íntrons/genética , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo , Fenótipo , Isoformas de Proteínas/deficiência , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas com Domínio T/deficiência , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Cauda/anatomia & histologia , Cauda/embriologia , Éxons/genética
2.
J Morphol ; 281(8): 938-955, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32515875

RESUMO

Shark skin denticles (scales) are diverse in morphology both among species and across the body of single individuals, although the function of this diversity is poorly understood. The extremely elongate and highly flexible tail of thresher sharks provides an opportunity to characterize gradients in denticle surface characteristics along the length of the tail and assess correlations between denticle morphology and tail kinematics. We measured denticle morphology on the caudal fin of three mature and two embryo common thresher sharks (Alopias vulpinus), and we compared thresher tail denticles to those of eleven other shark species. Using surface profilometry, we quantified 3D-denticle patterning and texture along the tail of threshers (27 regions in adults, and 16 regions in embryos). We report that tails of thresher embryos have a membrane that covers the denticles and reduces surface roughness. In mature thresher tails, surfaces have an average roughness of 5.6 µm which is smoother than some other pelagic shark species, but similar in roughness to blacktip, porbeagle, and bonnethead shark tails. There is no gradient down the tail in roughness for the middle or trailing edge regions and hence no correlation with kinematic amplitude or inferred magnitude of flow separation along the tail during locomotion. Along the length of the tail there is a leading-to-trailing-edge gradient with larger leading edge denticles that lack ridges (average roughness = 9.6 µm), and smaller trailing edge denticles with 5 ridges (average roughness = 5.7 µm). Thresher shark tails have many missing denticles visible as gaps in the surface, and we present evidence that these denticles are being replaced by new denticles that emerge from the skin below.


Assuntos
Ecossistema , Imageamento Tridimensional , Tubarões/anatomia & histologia , Cauda/anatomia & histologia , Animais , Fenômenos Biomecânicos , Calcificações da Polpa Dentária , Análise Discriminante , Embrião não Mamífero/anatomia & histologia , Embrião não Mamífero/ultraestrutura , Análise Multivariada , Tubarões/embriologia , Cauda/ultraestrutura
3.
Zoology (Jena) ; 139: 125745, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32106043

RESUMO

During spinal cord (SC) regeneration in the tail of Rana dalmatina tadpoles few neurons are regenerated from the ependymal epithelium. Using microscopic methods, immunofluorescence, tract tracing and electron microscopy, the present study has analyzed the cells generated in the caudal SC during the first 20 days of regeneration under normal and stress conditions. Since early larval stages, the regenerating SC contains few nerve cells (2-3%) and more numerous immune cells (5-7%), namely heterophil granulocytes, macrophages and lymphocytes. Few regenerated nerve cells are connected to the normal SC by axons detected after application of the retrograde fluorescent tracer Dil. Cell degeneration in the regenerating SC is commonly observed, including also loss of nerve cells, a process that occurs well in advance from metamorphosis. Furthermore, under lightly stress conditions, when tadpoles are kept in agitated water during tail regeneration, nerve degeneration and the number of immune cells significantly increases in the regenerating SC, a mean of 13.5% versus 5.6% in normal conditions. The study shows that normal and regenerating SC are under immune surveillance since early tadpole stages, well in advance of metamorphosis when immune cells determine the degeneration of the SC and the complete reabsorption of the tail.


Assuntos
Metamorfose Biológica/fisiologia , Ranidae/fisiologia , Regeneração/fisiologia , Medula Espinal/citologia , Cauda/fisiologia , Animais , Larva/fisiologia , Linfócitos/fisiologia , Macrófagos/fisiologia , Medula Espinal/fisiologia , Cauda/anatomia & histologia
4.
Genes Cells ; 25(2): 86-99, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31788928

RESUMO

Neurotrophic signaling regulates neural cell behaviors in development and physiology, although its role in regeneration has not been fully investigated. Here, we examined the role of neurotrophic signaling in Xenopus laevis tadpole tail regeneration. After the tadpole tails were amputated, the expression of neurotrophin ligand family genes, especially ngf and bdnf, was up-regulated as regeneration proceeded. Moreover, notochordal expression of the NGF receptor gene TrkA, but not that of other neurotrophin receptor genes TrkB and TrkC, became prominent in the regeneration bud, a structure arising from the tail stump after tail amputation. The regenerated tail length was significantly shortened by the pan-Trk inhibitor K252a or the TrkA inhibitor GW-441756, but not by the TrkB inhibitor ANA-12, suggesting that TrkA signaling is involved in elongation of regenerating tails. Furthermore, during Xenopus laevis embryonic development, TrkA expression was detected in the dorsal mesoderm at the gastrula stage and in the notochord at the neurula stage, and its knockdown led to gastrulation defects with subsequent shortening of the body axis length. These results suggest that Xenopus laevis TrkA signaling, which can act in the mesoderm/notochord, plays a key role in body axis elongation during embryogenesis as well as tail elongation during tadpole regeneration.


Assuntos
Desenvolvimento Embrionário/genética , Larva/genética , Receptor trkA/genética , Receptor trkA/metabolismo , Regeneração/genética , Transdução de Sinais , Cauda/fisiologia , Xenopus laevis/anormalidades , Xenopus laevis/genética , Animais , Azepinas/farmacologia , Benzamidas/farmacologia , Carbazóis/farmacologia , Regulação da Expressão Gênica no Desenvolvimento , Alcaloides Indólicos/farmacologia , Fator de Crescimento Neural/genética , Proteínas do Tecido Nervoso/genética , Receptor trkA/antagonistas & inibidores , Receptor trkC/genética , Receptores de Fator de Crescimento Neural/genética , Transdução de Sinais/efeitos dos fármacos , Cauda/anatomia & histologia
5.
Thromb Haemost ; 117(6): 1171-1181, 2017 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-28300869

RESUMO

Selectins, such as E-selectin (CD62E), function in venous thrombosis by binding and activating immune cells to initiate the coagulation cascade. GMI-1271 is a small molecule antagonist that inhibits E-selectin activity. Here we determine whether inhibition of E-selectin is sufficient to decrease acute venous thrombosis and associated inflammatory events in both prophylactic and treatment protocols without significantly affecting haemostasis. Male C57BL/6 mice underwent surgery for experimental thrombosis induction and were harvested at peak thrombus formation in our animal model, two days post induction. Groups included non-thrombosed true controls, shams, controls, and prophylactic or treatment groups of GMI-1271 (10 mg/kg intraperitoneal BID (twice a day) and low-molecular-weight heparin (LMWH, Lovenox 6 mg/kg subcutaneously (SC), once a day (SID). Compared with control animals, prophylaxis or treatment with LMWH and GMI-1271 in a dose-dependent manner significantly decreased thrombosis. GMI-1271 significantly lowered tail bleeding times when compared to LMWH. GMI-1271 and LMWH prophylactically administered significantly decreased vein wall neutrophil cell extravasation. However, all treatment and prophylactic therapies significantly decreased vein wall monocyte extravasation versus controls. GMI-1271 prophylactic therapy significantly decreased intra-thrombus cell counts versus control animals and other treatment groups. Immunohistochemistry confirmed that both treatments with GMI-1271 and LMWH significantly decreased activated leukocyte migration. GMI-1271 therapy significantly decreased thrombus weight and resulted in significantly lower bleeding times than LMWH. GMI-1271 treated mice showed decreased local and systemic inflammatory effects while modulating neutrophil activation, suggesting that GMI-1271 is a viable therapeutic candidate for venous thrombosis prophylaxis and treatment.


Assuntos
Selectina E/metabolismo , Gangliosídeos/uso terapêutico , Hemorragia/prevenção & controle , Inflamação/tratamento farmacológico , Neutrófilos/imunologia , Veias/fisiologia , Trombose Venosa/tratamento farmacológico , Animais , Antígeno CA-19-9 , Movimento Celular , Modelos Animais de Doenças , Selectina E/antagonistas & inibidores , Gangliosídeos/química , Hemorragia/etiologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mimetismo Molecular , Cauda/anatomia & histologia , Trombose Venosa/complicações
6.
Acta cir. bras ; 30(11): 743-748, Nov. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-767595

RESUMO

PURPOSE : To investigate allometric relationships among body mass (BM), muzzle-tail length (MTL), and tibia length (TL) in Wistar rats and establish their growth rate change parameters. METHODS : Eighteen male and 18 female Wistar rats were studied from the 3rd to the 21st week of age. BM, MTL, and TL were measured daily, and relative growth was compared using allometry. RESULTS : A positive correlation between BM and MTL (p<0.05) and BM and TL (p<0.05) was observed. Males and females showed comparable curves; however, females had turning points at a younger age. The allometric relationship between BM and MTL presented a regular increase until reaching a mass of 351 g (males) and 405 g (females). BM and TL showed an initial increase until 185 g (males) and 182 g (females), and then reached a plateau that finished at 412 g (males) and 334 g (females), to display another increase. CONCLUSIONS : The allometric relationship of body mass with animal length and tibia length was comparable for male and female rats, with female rats maturing earlier. Animal longitudinal growth occurred in a single stage. In contrast, tibia length depicted two stages of accelerated growth with an intermediate period of deceleration.


Assuntos
Animais , Feminino , Masculino , Tamanho Corporal/fisiologia , Peso Corporal/fisiologia , Ratos Wistar/crescimento & desenvolvimento , Cauda/crescimento & desenvolvimento , Tíbia/crescimento & desenvolvimento , Fatores Etários , Padrões de Referência , Fatores Sexuais , Fatores de Tempo , Cauda/anatomia & histologia , Tíbia/anatomia & histologia
7.
Arq. bras. med. vet. zootec ; 67(3): 909-917, May-Jun/2015. graf
Artigo em Português | LILACS | ID: lil-753909

RESUMO

A exploração comercial de jacaré-do-Pantanal (Caiman yacare) constitui importante cadeia produtiva no Estado de Mato Grosso. As características nutricionais e representatividade na massa corporal de crocodilianos tornaram a região da cauda objeto de estudos morfofisiológicos, evolutivos e tecnológicos. Como inexiste a caracterização anatômica dos músculos e ossos que constituem os cortes comerciais dessa região, objetivou-se descrever os músculos e correspondentes bases ósseas da cauda. Na descrição óssea, foram utilizados um exemplar adulto e seis juvenis. Para caracterização muscular, 24 espécimes juvenis foram conservados em freezer e dissecados a fresco, em ambos os antímeros, para verificação de simetria de ocorrência, fixações musculares, relacões de sintopia, forma e arquitetura muscular. As vértebras caudais são procélicas, exceto a primeira da série, e possuem na superfície ventral do corpo áreas para articulação com os processos hemais, exceto a primeira e as quatro ou cinco últimas. Os cortes comerciais da região são o filé de cauda, composto pelos músculos semiespinhal caudal, longuíssimo caudal, ilioisquiocaudal, caudofemoral longo, transverso e profundo da cauda, enquanto o corte ponta de cauda é constituído pelos músculos longuíssimo caudal e ilioisquiocaudal, com as cinco ou seis últimas vértebras caudais.


The commercial exploitation of the Yacare Caiman (Caiman yacare) has become a relevant commodity in the state of Mato Grosso, Brazil. Crocodilian's tail muscles nutritional characteristics and representativeness in body mass became the object of morphophysiological technological and evolutionary studies. The aim of this research was to report, for the first time, the anatomical characterization of muscle and bone bases of Pantanal Caiman meat cuts obtained from the tail. To describe the bones, we used one adult and six juvenile specimens of Pantanal Caiman. In order to study the muscle, 24 juvenile individuals were slaughtered and skinned, preserved in a -20oC freezer and thawed at the time of use, without any fixation. After evisceration, the specimens were dissected on both sides to verify structural symmetry, muscle attachments, sintopy relations, shape and muscular architecture. Caudal vertebrae are procoelous, except for the first of the series, and have sites on the ventral surface of their body where the hemal processes articulate, with the exception of the first and the last four or five vertebrae. The commercial meat cuts of the tail are the tail sirloin, composed of semispinal caudal, longissimus caudal, ilioischiocaudal, long caudofemoral, transverse and deep of the tail muscles, and also the tail tip, consisting of the longissimus caudal and ilioischiocaudal muscles, based on the last five or six caudal vertebrae.


Assuntos
Animais , Cauda/anatomia & histologia , Jacarés e Crocodilos/anatomia & histologia , Músculos/anatomia & histologia , Osso e Ossos/anatomia & histologia , Carne/classificação
8.
Annu Rev Cell Dev Biol ; 30: 535-60, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25062362

RESUMO

Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous.


Assuntos
Cães/genética , Genoma , Animais , Tamanho Corporal/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/veterinária , Cruzamento , Mapeamento Cromossômico , Modelos Animais de Doenças , Doenças do Cão/genética , Cães/anatomia & histologia , Cães/classificação , Extremidades/anatomia & histologia , Estudo de Associação Genômica Ampla , Glicoproteínas/genética , Glicoproteínas/fisiologia , Proteína HMGA2/genética , Proteína HMGA2/fisiologia , Cabelo/anatomia & histologia , Cardiopatias/genética , Cardiopatias/veterinária , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/veterinária , Osteossarcoma/genética , Osteossarcoma/veterinária , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Seleção Genética , Pele/anatomia & histologia , Crânio/anatomia & histologia , Proteína Smad2/genética , Proteína Smad2/fisiologia , Especificidade da Espécie , Cauda/anatomia & histologia
9.
Physiol Behav ; 129: 1-10, 2014 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-24560842

RESUMO

The main goals of this study were to classify dams according to the level of voluntary physical activity before breeding and during pregnancy/lactation and to evaluate the effects on growth trajectory and reflex ontogenesis of offspring. Voluntary physical activity was ranked by traveled distance, time and daily estimated calorie burned. Thirty-five female Wistar rats were classified as control (C, n=5), inactive (I, n=10), active (A, n=8) and very active (VA, n=12). During 30d before breeding, traveled distance, average speed, time and calorie burned were daily recorded for active and very active groups. Traveled distance was recorded each 2h every day of adaptation. Body weight, food intake and fasting glycemia were measured throughout the experiment. During lactation, litters were evaluated in terms of physical features and reflex ontogeny. VA showed a progressive increase in the traveled distance and time while A dams presented constant values. VA rats showed lower body weight and higher food intake. During pregnancy, both groups performed less than 1km/day. Pups from A and VA dams showed higher lateral-lateral axis of the skull, longitudinal axis, tail length, and anticipation of the pavilion and auditory canal opening, and erupting incisors. I, A and VA groups showed a delay of righting, cliff aversion and vibrissae placing reflexes. In conclusion, active maternal phenotype is established before breeding allowing mothers to fit ecological and influencing growth trajectory outcomes and reflex ontogeny of the offspring based on matrilineal experience.


Assuntos
Crescimento e Desenvolvimento , Comportamento Materno , Atividade Motora , Reflexo , Animais , Peso Corporal , Meato Acústico Externo/crescimento & desenvolvimento , Ingestão de Alimentos , Comportamento Exploratório , Feminino , Incisivo/crescimento & desenvolvimento , Locomoção , Tamanho do Órgão , Fenótipo , Ratos , Ratos Wistar , Crânio/anatomia & histologia , Crânio/crescimento & desenvolvimento , Cauda/anatomia & histologia
10.
Mamm Genome ; 24(9-10): 400-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23949773

RESUMO

Most mammals possess a tail, humans and the Great Apes being notable exceptions. One approach to understanding the mechanisms and evolutionary forces influencing development of a tail is to identify the genetic factors that influence extreme tail length variation within a species. In mice, the Tailless locus has proven to be complex, with evidence of multiple different genes and mutations with pleiotropic effects on tail length, fertility, embryogenesis, male transmission ratio, and meiotic recombination. Five cat breeds have abnormal tail length phenotypes: the American Bobtail, the Manx, the Pixie-Bob, the Kurilian Bobtail, and the Japanese Bobtail. We sequenced the T gene in several independent lineages of Manx cats from both the US and the Isle of Man and identified three 1-bp deletions and one duplication/deletion, each predicted to cause a frameshift that leads to premature termination and truncation of the carboxy terminal end of the Brachyury protein. Ninety-five percent of Manx cats with short-tail phenotypes were heterozygous for T mutations, mutant alleles appeared to be largely lineage-specific, and a maximum LOD score of 6.21 with T was obtained at a recombination fraction (Θ) of 0.00. One mutant T allele was shared with American Bobtails and Pixie-Bobs; both breeds developed more recently in the US. The ability of mutant Brachyury protein to activate transcription of a downstream target was substantially lower than wild-type protein. Collectively, these results suggest that haploinsufficiency of Brachyury is one mechanism underlying variable tail length in domesticated cats.


Assuntos
Proteínas Fetais/genética , Proteínas com Domínio T/genética , Cauda/anatomia & histologia , Alelos , Sequência de Aminoácidos , Animais , Gatos , Linhagem Celular Tumoral , Feminino , Proteínas Fetais/química , Frequência do Gene , Estudos de Associação Genética , Haploinsuficiência , Escore Lod , Masculino , Camundongos , Dados de Sequência Molecular , Linhagem , Fenótipo , Análise de Sequência de DNA , Deleção de Sequência , Proteínas com Domínio T/química
11.
J Exp Biol ; 216(Pt 6): 1031-40, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23447666

RESUMO

A major roadblock in the biomedical treatment of human sensory disorders, including blindness, has been an incomplete understanding of the nervous system and its ability to adapt to changes in sensory modality. Likewise, fundamental insight into the evolvability of complex functional anatomies requires understanding brain plasticity and the interaction between the nervous system and body architecture. While advances have been made in the generation of artificial and biological replacement components, the brain's ability to interpret sensory information arising from ectopic locations is not well understood. We report the use of eye primordia grafts to create ectopic eyes along the body axis of Xenopus tadpoles. These eyes are morphologically identical to native eyes and can be induced at caudal locations. Cell labeling studies reveal that eyes created in the tail send projections to the stomach and trunk. To assess function we performed light-mediated learning assays using an automated machine vision and environmental control system. The results demonstrate that ectopic eyes in the tail of Xenopus tadpoles could confer vision to the host. Thus ectopic visual organs were functional even when present at posterior locations. These data and protocols demonstrate the ability of vertebrate brains to interpret sensory input from ectopic structures and incorporate them into adaptive behavioral programs. This tractable new model for understanding the robust plasticity of the central nervous system has significant implications for regenerative medicine and sensory augmentation technology.


Assuntos
Coristoma , Modelos Animais , Plasticidade Neuronal/fisiologia , Fenômenos Fisiológicos Oculares , Cauda/anatomia & histologia , Visão Ocular/fisiologia , Xenopus laevis/fisiologia , Análise de Variância , Animais , Olho/anatomia & histologia , Larva/anatomia & histologia , Microcirurgia , Vias Neurais/fisiologia , Xenopus laevis/anatomia & histologia
12.
J Bone Miner Res ; 28(4): 899-911, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23129509

RESUMO

Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2 D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Compostos de Fenilureia/farmacologia , Pirimidinas/farmacologia , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Raquitismo Hipofosfatêmico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Desenvolvimento Ósseo/efeitos dos fármacos , Proteínas da Matriz Extracelular/deficiência , Proteínas da Matriz Extracelular/metabolismo , Fêmur/efeitos dos fármacos , Fêmur/patologia , Fator de Crescimento de Fibroblastos 23 , Lâmina de Crescimento/efeitos dos fármacos , Lâmina de Crescimento/patologia , Homeostase/efeitos dos fármacos , Íons , Rim/efeitos dos fármacos , Rim/metabolismo , Camundongos Endogâmicos C57BL , Minerais/metabolismo , Compostos de Fenilureia/uso terapêutico , Pirimidinas/uso terapêutico , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Raquitismo Hipofosfatêmico/tratamento farmacológico , Raquitismo Hipofosfatêmico/patologia , Cauda/anatomia & histologia , Vitamina D/análogos & derivados , Vitamina D/biossíntese
13.
Cold Spring Harb Protoc ; 2012(11): 1177-8, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23118364

RESUMO

The lymphatic system is an important route for metastasis of cancer cells. Lymphatic microvessels have been studied by adapting lymphangiography to the mouse tail. In this technique, a high-molecular-weight fluorescently labeled tracer is injected into the interstitial compartment of the tail tissue. The tracer migrates to the local lymphatic vessels and fills the network, allowing visualization. By implanting a tumor in the tail, the structure and function of the lymphatics at the tumor periphery can be monitored. This protocol describes a method for injecting tumor cells into a mouse tail and for microlymphangiography.


Assuntos
Linfografia/métodos , Cauda/anatomia & histologia , Animais , Corantes Fluorescentes/administração & dosagem , Camundongos , Coloração e Rotulagem/métodos
14.
Anat Rec (Hoboken) ; 295(2): 289-97, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22095903

RESUMO

Elongate body forms have evolved numerous times independently within Vertebrata. Such body forms have evolved in large part via changes to the vertebral column, either through addition or lengthening of vertebrae. Previous studies have shown that body elongation in fishes has evolved most frequently through the addition of caudal vertebrae. In contrast, however, body elongation in Polypteriformes, a basal clade of ray-finned fishes (Actinopterygii), has evolved through the addition of precaudal vertebrae; one genus, Erpetoichthys, has approximately twice as many precaudal vertebrae as do members of its sister genus, Polypterus. Thus, polypteriform fishes provide an excellent opportunity to study the effects of precaudal elongation on the gross morphology and organization of visceral organs contained within the body cavity. In this study, we document the anteroposterior positions of most major visceral organs in representative species of both genera (E. calabaricus and P. palmas), relative to both vertebral number and percent pre-anal length. We found that, whereas the positions of the anterior and posterior borders of the visceral organs relative to percent pre-anal length were generally similar between the two species, most visceral organs were positioned further posteriorly in E. calabaricus than in P. palmas with respect to vertebral number. Based on previous determinations of the molecular control of anteroposterior patterning of the visceral organs, we discuss which possible changes in gene expression may have led to the anatomical modifications seen in the visceral morphology of Erpetoichthys.


Assuntos
Padronização Corporal , Peixes/anatomia & histologia , Trato Gastrointestinal/anatomia & histologia , Vísceras/anatomia & histologia , Animais , Evolução Biológica , Regulação da Expressão Gênica no Desenvolvimento , Especificidade da Espécie , Coluna Vertebral/anatomia & histologia , Cauda/anatomia & histologia
15.
Am J Physiol Cell Physiol ; 302(2): C392-404, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21940662

RESUMO

Lymphangiogenic cytokines such as vascular endothelial growth factor-C (VEGF-C) are critically required for lymphatic regeneration; however, in some circumstances, lymphatic function is impaired despite normal or elevated levels of these cytokines. The recent identification of anti-lymphangiogenic molecules such as interferon-γ (IFN-γ), transforming growth factor-ß1, and endostatin has led us to hypothesize that impaired lymphatic function may represent a dysregulated balance in the expression of pro/anti-lymphangiogenic stimuli. We observed that nude mice have significantly improved lymphatic function compared with wild-type mice in a tail model of lymphedema. We show that gradients of lymphatic fluid stasis regulate the expression of lymphangiogenic cytokines (VEGF-A, VEGF-C, and hepatocyte growth factor) and that paradoxically the expression of these molecules is increased in wild-type mice. More importantly, we show that as a consequence of T-cell-mediated inflammation, these same gradients also regulate expression patterns of anti-lymphangiogenic molecules corresponding temporally and spatially with impaired lymphatic function in wild-type mice. We show that neutralization of IFN-γ significantly increases inflammatory lymph node lymphangiogenesis independently of changes in VEGF-A or VEGF-C expression, suggesting that alterations in the balance of pro- and anti-lymphangiogenic cytokine expression can regulate lymphatic vessel formation. In conclusion, we show that gradients of lymphatic fluid stasis regulate not only the expression of pro-lymphangiogenic cytokines but also potent suppressors of lymphangiogenesis as a consequence of T-cell inflammation and that modulation of the balance between these stimuli can regulate lymphatic function.


Assuntos
Citocinas/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Linfangiogênese/fisiologia , Sistema Linfático/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Animais , Feminino , Inflamação/metabolismo , Inflamação/patologia , Interferon gama/antagonistas & inibidores , Interferon gama/metabolismo , Linfa/metabolismo , Sistema Linfático/patologia , Sistema Linfático/fisiopatologia , Linfedema/metabolismo , Linfedema/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Regeneração/fisiologia , Linfócitos T/imunologia , Cauda/anatomia & histologia , Cauda/metabolismo , Cauda/patologia , Cauda/fisiopatologia
16.
An. acad. bras. ciênc ; 83(1): 61-72, Mar. 2011. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-578282

RESUMO

Missing data is a common problem in paleontology. It makes it difficult to reconstruct extinct taxa accurately and restrains the inclusion of some taxa on comparative and biomechanical studies. Particularly, estimating the position of vertebrae on incomplete series is often non-empirical and does not allow precise estimation of missing parts. In this work we present a method for calculating the position of preserved middle sequences of caudal vertebrae in the saurischian dinosaur Staurikosaurus pricei, based on the length and height of preserved anterior and posterior caudal vertebral centra. Regression equations were used to estimate these dimensions for middle vertebrae and, consequently, to assess the position of the preserved middle sequences. It also allowed estimating these dimensions for non-preserved vertebrae. Results indicate that the preserved caudal vertebrae of Staurikosaurus may correspond to positions 1-3, 5, 7, 14-19/15-20, 24-25/25-26, and 29-47, and that at least 25 vertebrae had transverse processes. Total length of the tail was estimated in 134 cm and total body length was 220-225 cm.


Dados lacunares são um problema comum na paleontologia. Eles dificultam a reconstrução acurada de táxons extintos e limitam a inclusão de alguns táxons em estudos comparativose biomecânicos. Particularmente, estimar a posição de vértebras em séries incompletas tem sido feito com base em métodos não empíricos que não permitem estimar corretamente as partes ausentes. Neste trabalho apresentamos uma metodologia que permite estimar a posição de sequências médias preservadas de vértebras caudais no dinossauro saurísquio Staurikosaurus pricei, com base no comprimento e altura dos centros das vértebras anteriores e posteriores preservadas. Equações de regressão foram usadas para estimar essas dimensões para as vértebras médias e, consequentemente, para posicionar as sequências médias preservadas e para estimar o tamanho das vértebras não preservadas. Os resultados indicam que as vértebras caudais preservadas de Staurikosaurus corresponderiam às posições 1-3, 5, 7, 14-19/15-20, 24-25/25-26 e 29-47, e que pelo menos 25 vértebras possuíam processos transversos. O comprimento total da cauda foi estimado em 134 cm e o comprimento total do corpo em 220-225 cm.


Assuntos
Animais , Dinossauros/anatomia & histologia , Paleontologia/métodos , Coluna Vertebral/anatomia & histologia , Cauda/anatomia & histologia , Dinossauros/classificação , Fósseis
17.
An. acad. bras. ciênc ; 83(1): 309-315, Mar. 2011. ilus
Artigo em Inglês | LILACS | ID: lil-578298

RESUMO

An isolated pterosaurian caudal cervical (~ postcervical) vertebra was recovered from the Upper Cretaceous Lapurr sandstone ofWest Turkana, northwestern Kenya. The vertebral centrum is short, wide, and dorsoventrally compressed. Although the specimen is lightly built similar to most pterosaurs, it is here referred to Pterodactyloidea and tentatively to the Azhdarchidae in that it lacks pneumatic features on both the centrum and neural arch. This represents one of the few pterosaurs recovered from the entirety of Afro-Arabia, the first pterosaur recovered from the Cretaceous of East Africa, and, significantly, a specimen that was recovered from fluvial deposits rather than the near-shore marine setting typical of most pterosaur discoveries.


Uma vértebra cervical caudal isolada de pterossauro (~ pós-cervical) foi recuperada do Cretáceo Superior do arenito de Lapurr do Oeste de Turkana, noroeste do Quênia. O centro vertebral é curto, largo e comprimido dorsoventralmente. Embora o espécime seja leve como grande parte dos pterossauros, ele é aqui referido a Pterodactyloidea e tentativamente a Azhdarchidae no que diz respeito à ausência de características pneumáticas tanto no centro quanto no arco neural. Este representa um dos poucos pterossauros recuperados do conjunto Afro-Arábia, o primeiro pterossauro proveniente do Cretáceo do Leste da África e, significativamente, um espécime que foi recuperado de depósitos fluviais e não do cenário marinho próximo da costa típico da maioria das descobertas de pterossauros.


Assuntos
Animais , Vértebras Cervicais/anatomia & histologia , Dinossauros/anatomia & histologia , Dinossauros/classificação , Fósseis , Cauda/anatomia & histologia , Brasil , Quênia
18.
Naturwissenschaften ; 97(7): 645-53, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20533021

RESUMO

In fish the neuromasts of the lateral line develop as follows: a "migrating primordium" (MP) migrates from the postotic placode along the future posterior lateral line canal to the tail fin. Its placodal cells are assumed to be the basis for the development of the neuromasts. However, an MP was not found in all fish, e.g., in catfish. In the present study, a search was made for the MP in the larvae of the catfish Silurus glanis. Using light and electron microscopy, an MP was found to migrate along the ventral rim of the tail. It precedes the formation of a ventral row of free neuromasts. An MP preceding the main lateral row of the future canal neuromasts was not found. The necessity of the MP for the ventral-free neuromast development is shown by making incisions which block its migration. The result: caudal to the incision site neuromasts do not develop. On the other hand, the same incision procedure applied to the assumed migration route of a--hypothetical--lateral MP does not block the development of the lateral neuromasts. It is concluded that in this case an MP is not necessary for the development of the canal neuromasts.


Assuntos
Peixes-Gato/crescimento & desenvolvimento , Sistema da Linha Lateral/fisiologia , Mecanorreceptores/fisiologia , Animais , Peixes-Gato/fisiologia , Sistema da Linha Lateral/crescimento & desenvolvimento , Mecanorreceptores/ultraestrutura , Cauda/anatomia & histologia , Cauda/fisiologia
19.
Development ; 136(17): 2987-96, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19666825

RESUMO

Tail regeneration in Xenopus tadpoles is a favorable model system to understand the molecular and cellular basis of tissue regeneration. Although turnover of the extracellular matrix (ECM) is a key event during tissue injury and repair, no functional studies to evaluate its role in appendage regeneration have been performed. Studying the role of Hyaluronan (HA), an ECM component, is particularly attractive because it can activate intracellular signaling cascades after tissue injury. Here we studied the function of HA and components of the HA pathway in Xenopus tadpole tail regeneration. We found that transcripts for components of this pathway, including Hyaluronan synthase2 (HAS2), Hyaluronidase2 and its receptors CD44 and RHAMM, were transiently upregulated in the regenerative bud after tail amputation. Concomitantly, an increase in HA levels was observed. Functional experiments using 4-methylumbelliferone, a specific HAS inhibitor that blocked the increase in HA levels after tail amputation, and transgenesis demonstrated that the HA pathway is required during the early phases of tail regeneration. Proper levels of HA are required to sustain proliferation of mesenchymal cells in the regenerative bud. Pharmacological and genetic inhibition of GSK3beta was sufficient to rescue proliferation and tail regeneration when HA synthesis was blocked, suggesting that GSK3beta is downstream of the HA pathway. We have demonstrated that HA is an early component of the regenerative pathway and is required for cell proliferation during the early phases of Xenopus tail regeneration. In addition, a crosstalk between HA and GSK3beta signaling during tail regeneration was demonstrated.


Assuntos
Ácido Hialurônico/metabolismo , Larva , Regeneração/fisiologia , Cauda/fisiologia , Xenopus laevis , Animais , Animais Geneticamente Modificados , Proliferação de Células , Regulação da Expressão Gênica no Desenvolvimento , Glucuronosiltransferase/antagonistas & inibidores , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Hialuronan Sintases , Ácido Hialurônico/genética , Himecromona/análogos & derivados , Himecromona/metabolismo , Larva/anatomia & histologia , Larva/fisiologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Transdução de Sinais/fisiologia , Cauda/anatomia & histologia , Proteínas de Xenopus/antagonistas & inibidores , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis/anatomia & histologia , Xenopus laevis/fisiologia
20.
Zoolog Sci ; 26(2): 119-24, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19341328

RESUMO

Certain plastic morphological responses of animals induced across a range of environmental conditions may be adapted for effective locomotor performance. Larvae of the salamander, Hynobius retardatus, occasionally swim upward to the surface to breathe air because aquatic respiration alone is insufficient to meet their increasing respiratory requirements for growth. We hypothesized that H. retardatus larvae living in deep water would show an induced plastic response affecting locomotor structures, namely, a deeper tail, similar to that induced by predatory dragonfly larvae (Aeschna juncea), to improve their swimming performance. In this study, larval salamanders responded similarly to different cues (waterborne chemicals in a predatory environment and distance to the water's surface) by developing deeper tails. The similar modifications in tail shape presumably increase a larva's swimming performance, thereby improving its ability both to escape an attacking predator and to swim to the surface for air. The response in tail shape induced by the predatory environment was rapid, but was more gradual in larvae raised in deep water, suggesting that animals may quickly assess a dangerous environment and immediately respond, whereas assessment of an environment not requiring an immediate response for survival may be slower, accounting for the delayed response.


Assuntos
Comportamento Predatório/fisiologia , Natação/fisiologia , Cauda/fisiologia , Urodelos/fisiologia , Animais , Sinais (Psicologia) , Cauda/anatomia & histologia , Urodelos/anatomia & histologia
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