Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Microbiol Immunol ; 67(10): 429-437, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37461376

RESUMO

The high mortality rate associated with Listeria monocytogenes can be attributed to its ability to invade the body systemically and to activate inflammasomes. Both of these processes are facilitated by expressing a major virulence factor known as listeriolysin O, a 56 kDa pore-forming protein encoded by the hly gene. Listeriolysin O plays a crucial role in the pathogenesis of the bacterium by facilitating the escape of the pathogen from the phagosome into the cytosol. This process is essential for the successful establishment of infection. In addition, listeriolysin O is known as an immunomodulator that activates host signal transduction. In addition to listeriolysin O, Listeria expresses a variety of bacterial ligands, such as lipoteichoic acid, nucleotide, and flagellin, that are recognized by host intracellular pattern-recognition receptors including Nod-like receptors, AIM2-like receptors, and RIG-I-like receptors. This review introduces intracellular recognition of Listeria monocytogenes since recent studies have revealed that the activation of inflammasome exacerbates Gram-positive bacteria infection.


Assuntos
Listeria monocytogenes , Listeriose , Humanos , Inflamassomos/metabolismo , Proteínas Hemolisinas/genética , Fagossomos/metabolismo , Fagossomos/microbiologia , Fagossomos/patologia , Citosol , Fatores de Virulência/metabolismo
2.
Nat Immunol ; 22(7): 820-828, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33976430

RESUMO

Efficient immune responses against viral infection are determined by sufficient activation of nucleic acid sensor-mediated innate immunity1,2. Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains an ongoing global pandemic. It is an urgent challenge to clarify the innate recognition mechanism to control this virus. Here we show that retinoic acid-inducible gene-I (RIG-I) sufficiently restrains SARS-CoV-2 replication in human lung cells in a type I/III interferon (IFN)-independent manner. RIG-I recognizes the 3' untranslated region of the SARS-CoV-2 RNA genome via the helicase domains, but not the C-terminal domain. This new mode of RIG-I recognition does not stimulate its ATPase, thereby aborting the activation of the conventional mitochondrial antiviral-signaling protein-dependent pathways, which is in accordance with lack of cytokine induction. Nevertheless, the interaction of RIG-I with the viral genome directly abrogates viral RNA-dependent RNA polymerase mediation of the first step of replication. Consistently, genetic ablation of RIG-I allows lung cells to produce viral particles that expressed the viral spike protein. By contrast, the anti-SARS-CoV-2 activity was restored by all-trans retinoic acid treatment through upregulation of RIG-I protein expression in primary lung cells derived from patients with chronic obstructive pulmonary disease. Thus, our findings demonstrate the distinctive role of RIG-I as a restraining factor in the early phase of SARS-CoV-2 infection in human lung cells.


Assuntos
COVID-19/imunologia , Proteína DEAD-box 58/imunologia , Pulmão/imunologia , Receptores Imunológicos/imunologia , SARS-CoV-2/imunologia , Células A549 , Animais , Linhagem Celular , Linhagem Celular Tumoral , Chlorocebus aethiops , Cães , Células HEK293 , Humanos , Interferon Tipo I/imunologia , Interferons/imunologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Doença Pulmonar Obstrutiva Crônica/imunologia , RNA Polimerase Dependente de RNA/imunologia , Células Sf9 , Transdução de Sinais/imunologia , Células Vero , Proteínas Virais/imunologia , Interferon lambda
3.
Cell Rep ; 26(5): 1213-1226.e7, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30699350

RESUMO

Pancreatic ß cells secrete insulin by Ca2+-triggered exocytosis. However, there is no apparent secretory site similar to the neuronal active zones, and the cellular and molecular localization mechanism underlying polarized exocytosis remains elusive. Here, we report that ELKS, a vertebrate active zone protein, is used in ß cells to regulate Ca2+ influx for insulin secretion. ß cell-specific ELKS-knockout (KO) mice showed impaired glucose-stimulated first-phase insulin secretion and reduced L-type voltage-dependent Ca2+ channel (VDCC) current density. In situ Ca2+ imaging of ß cells within islets expressing a membrane-bound G-CaMP8b Ca2+ sensor demonstrated initial local Ca2+ signals at the ELKS-localized vascular side of the ß cell plasma membrane, which were markedly decreased in ELKS-KO ß cells. Mechanistically, ELKS directly interacted with the VDCC-ß subunit via the GK domain. These findings suggest that ELKS and VDCCs form a potent insulin secretion complex at the vascular side of the ß cell plasma membrane for polarized Ca2+ influx and first-phase insulin secretion from pancreatic islets.


Assuntos
Cálcio/metabolismo , Células Secretoras de Insulina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Subunidades Proteicas/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Glucose/farmacologia , Humanos , Insulina/metabolismo , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Ativação do Canal Iônico/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Proteínas do Tecido Nervoso/deficiência , Ligação Proteica/efeitos dos fármacos , Proteínas rab de Ligação ao GTP/deficiência
4.
Parkinsonism Relat Disord ; 61: 57-63, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30528172

RESUMO

INTRODUCTION: Glucocerebrosidase gene (GBA) variants are associated with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The molecular mechanisms underlying these diseases with GBA variants, however, are not well understood. In order to determine the effect of a deletion mutation in GBA, we performed a neuroimaging, genetic, and enzymatic study in a Japanese family with a gross deletion of exons 3 to 11 in GBA. METHODS: We performed [123I] FP-CIT SPECT and [123I] N-isopropyl-p-iodoamphetamine SPECT (IMP-SPECT), and determined GBA expression and glucocerebrosidase (GCase) activity in leukocytes in two GBA-associated PD patients and nine unaffected individuals (including four mutation carriers) in a Japanese family with a heterozygous gross deletion mutation in the GBA gene. RESULTS: The two PD patients and two of the four clinically unaffected carriers showed decreased [123I] FP-CIT uptake. IMP-SPECT showed a pattern like that in DLB in one patient. When we compared PD patients with GBA mutations with clinically unaffected carriers, there was a poor correlation between the development of PD and the expression level of GBA or GCase activity. CONCLUSION: We confirmed the gross deletion mutation in the GBA gene, which appeared to be associated with the PD or reduced [123I] FP-CIT in this family. However, since we cannot conclude whether a reduction of GCase activity is directly correlated with the pathogenesis of PD or not, longitudinal follow-up of this family is needed.


Assuntos
Encéfalo/diagnóstico por imagem , Glucosilceramidase/genética , Doença de Parkinson/genética , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Éxons , Família , Feminino , Deleção de Genes , Glucosilceramidase/metabolismo , Humanos , Iofetamina , Japão , Leucócitos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/enzimologia , Linhagem , Compostos Radiofarmacêuticos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tomografia Computadorizada de Emissão de Fóton Único , Tropanos
5.
Nat Cell Biol ; 19(5): 530-541, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28414314

RESUMO

Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells. Furthermore, EDAC from the surrounding normal cells, involving filamin, drives the Warburg-effect-like metabolic alteration. Moreover, using a cell-competition mouse model, we demonstrate that PDK-mediated metabolic changes promote the elimination of RasV12-transformed cells from intestinal epithelia. These data indicate that non-cell-autonomous metabolic modulation is a crucial regulator for cell competition, shedding light on the unexplored events at the initial stage of carcinogenesis.


Assuntos
Comunicação Celular , Transformação Celular Neoplásica/metabolismo , Metabolismo Energético , Células Epiteliais/metabolismo , Animais , Linhagem Celular Transformada , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Técnicas de Cocultura , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Cães , Feminino , Genes ras , Glucose/metabolismo , Glicólise , Ácido Láctico/metabolismo , Células Madin Darby de Rim Canino , Masculino , Potencial da Membrana Mitocondrial , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Interferência de RNA , Transdução de Sinais , Técnicas de Cultura de Tecidos , Transfecção
6.
Sci Rep ; 5: 15336, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26480891

RESUMO

Recent studies have revealed that cell competition can occur between normal and transformed epithelial cells; normal epithelial cells recognize the presence of the neighboring transformed cells and actively eliminate them from epithelial tissues. Here, we have established a brand-new high-throughput screening platform that targets cell competition. By using this platform, we have identified Rebeccamycin as a hit compound that specifically promotes elimination of RasV12-transformed cells from the epithelium, though after longer treatment it shows substantial cytotoxic effect against normal epithelial cells. Among several Rebeccamycin-derivative compounds, we have found that VC1-8 has least cytotoxicity against normal cells but shows the comparable effect on the elimination of transformed cells. This cell competition-promoting activity of VC1-8 is observed both in vitro and ex vivo. These data demonstrate that the cell competition-based screening is a promising tool for the establishment of a novel type of cancer preventive medicine.


Assuntos
Transformação Celular Neoplásica/genética , Ensaios de Seleção de Medicamentos Antitumorais , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Genes ras , Ensaios de Triagem em Larga Escala , Bibliotecas de Moléculas Pequenas , Animais , Carbazóis/farmacologia , Comunicação Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Transformada , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo
7.
Cell Res ; 22(11): 1527-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22525337

RESUMO

It is not clearly understood what happens at the interface between normal and transformed epithelial cells at the first step of carcinogenesis. A recent study reveals that the organized epithelial structure suppresses clonal expansion of transformed cells. Translocation from the epithelium or perturbation of intercellular adhesions may be required for transformed cells to evade the suppressive environments.


Assuntos
Transformação Celular Neoplásica , Células Epiteliais/fisiologia , Neoplasias/patologia , Animais , Adesão Celular , Linhagem Celular , Microambiente Celular , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Células Epiteliais/citologia , Humanos , Inibidores de Metaloproteinases de Matriz , Metaloproteinases da Matriz/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/biossíntese , Receptor ErbB-2/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
8.
Biochem Biophys Res Commun ; 409(4): 705-10, 2011 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-21621510

RESUMO

In cranial skeletal development, the establishment of the ectomesenchymal lineage within the cranial neural crest is of great significance. Fgfs are polypeptide growth factors with diverse functions in development and metabolism. Fgf20b knockdown zebrafish embryos showed dysplastic neurocranial and pharyngeal cartilages. Ectomesenchymal cells from cranial neural crest cells were significantly decreased in Fgf20b knockdown embryos, but cranial neural crest cells with a non-ectomesnchymal fate were increased. However, the proliferation and apoptosis of cranial neural crest cells were essentially unchanged. Fgfr1 knockdown embryos also showed dysplastic neurocranial and pharyngeal cartilages. The present findings indicate that Fgf20b is required for ectomesenchymal fate establishment via the activation of Fgfr1 in zebrafish.


Assuntos
Ectoderma/citologia , Fatores de Crescimento de Fibroblastos/metabolismo , Mesoderma/citologia , Crista Neural/citologia , Crânio/embriologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Linhagem da Célula , Ectoderma/metabolismo , Cartilagem Elástica/embriologia , Cartilagem Elástica/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Técnicas de Silenciamento de Genes , Mesoderma/metabolismo , Crista Neural/metabolismo , Faringe/embriologia , Faringe/metabolismo , Crânio/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética
9.
Artif Life ; 16(4): 271-87, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20662598

RESUMO

Deacon has suggested that one of the key factors of language evolution is not characterized by an increase in genetic contribution, often known as the Baldwin effect, but rather by a decrease. This process effectively increases linguistic learning capability by organizing a novel synergy of multiple lower-order functions previously irrelevant to the process of language acquisition. Deacon posits that this transition is not caused by natural selection. Rather, it is due to the relaxation of natural selection. While there are some cases in which relaxation caused by some external factors indeed induces the transition, we do not know what kind of relaxation has worked in language evolution. In this article, a genetic-algorithm-based computer simulation is used to investigate how the niche-constructing aspect of linguistic behavior may trigger the degradation of genetic predisposition related to language learning. The results show that agents initially increase their genetic predisposition for language learning­the Baldwin effect. They create a highly uniform sociolinguistic environment­a linguistic niche construction. This means that later generations constantly receive very similar inputs from adult agents, and subsequently the selective pressure to retain the genetic predisposition is relaxed.


Assuntos
Evolução Molecular , Desenvolvimento da Linguagem , Idioma , Adulto , Algoritmos , Cromossomos Humanos/genética , Cognição/fisiologia , Cultura , Humanos , Conhecimento , Aprendizagem
10.
FEBS Lett ; 583(22): 3643-8, 2009 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-19852960

RESUMO

We identified a gene encoding a novel secreted protein in mice, humans, and zebrafish. As the protein of 222 amino acids is similar to Brorin, a secreted BMP antagonist, which is a member of the Chordin family, we named it Brorin-like. Recombinant Brorin-like protein weakly but significantly inhibited the activity of BMP in mouse preosteoblastic cells and promoted neurogenesis in mouse neural precursor cells. Brorin-like was predominantly expressed in the adult brain and embryonic neural tissues. The inhibition of Brorin-like functions in zebrafish resulted in the impairment of neural development. Brorin-like potentially plays roles in neural development and functions.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Glicoproteínas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Proteínas de Peixe-Zebra/genética , Células 3T3 , Sequência de Aminoácidos , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Células COS , Diferenciação Celular/genética , Células Cultivadas , Chlorocebus aethiops , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Glicoproteínas/metabolismo , Glicoproteínas/farmacologia , Humanos , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Camundongos , Dados de Sequência Molecular , Neurônios/citologia , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
11.
Dev Biol ; 332(1): 177-85, 2009 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-19481538

RESUMO

Fgf signaling plays essential roles in many developmental events. To investigate the roles of Fgf4 signaling in zebrafish development, we generated Fgf4 knockdown embryos by injection with Fgf4 antisense morpholino oligonucleotides. Randomized LR patterning of visceral organs including the liver, pancreas, and heart was observed in the knockdown embryos. Prominent expression of Fgf4 was observed in the posterior notochord and Kupffer's vesicle region in the early stages of segmentation. Lefty1, lefty2, southpaw, and pitx2 are known to play crucial roles in LR patterning of visceral organs. Fgf4 was essential for the expression of lefty1, which is necessary for the asymmetric expression of southpaw and pitx2 in the lateral plate mesoderm, in the posterior notochord, and the expression of lefty2 and lefty1 in the left cardiac field. Fgf8 is also known to be crucial for the formation of Kupffer's vesicle, which is needed for the LR patterning of visceral organs. In contrast, Fgf4 was required for the formation of cilia in Kupffer's vesicle, indicating that the role of Fgf4 in the LR patterning is quite distinct from that of Fgf8. The present findings indicate that Fgf4 plays a unique role in the LR patterning of visceral organs in zebrafish.


Assuntos
Padronização Corporal , Fatores de Crescimento de Fibroblastos/metabolismo , Vísceras/embriologia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Cílios/metabolismo , Embrião não Mamífero/citologia , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Coração/embriologia , Fatores de Determinação Direita-Esquerda , Fígado/embriologia , Fígado/metabolismo , Mesoderma/metabolismo , Notocorda/metabolismo , Pâncreas/embriologia , Pâncreas/metabolismo , Vísceras/metabolismo , Peixe-Zebra/genética
12.
Biochem J ; 419(2): 387-99, 2009 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-19125692

RESUMO

CS (chondroitin sulfate) has been implicated in a variety of biological processes during development. Its biological functions are closely associated with characteristic sulfated structures. Here, we report the characterization of a zebrafish counterpart of C4ST-1 (chondroitin 4-O-sulfotransferase-1) and its functional importance in embryogenesis. Recombinant C4ST-1 showed a substrate preference for chondroitin and catalysed the 4-O-sulfation of GalNAc residues, a highly frequent modification of CS in the embryos of zebrafish as well as other vertebrates. Whole-mount in situ hybridization revealed that C4ST-1 showed a distinct spatiotemporal expression pattern in the developing zebrafish embryo. During the segmentation stages, strong expression was observed along the body axis including the notochord and somites. Functional knockdown of C4ST-1 with specific antisense morpholino-oligonucleotides led to a marked decrease in the 4-O-sulfation and amount of CS in the embryos. Consistent with the preferential expression in the rostrocaudal axis, C4ST-1 morphants displayed morphological defects exemplified by a ventrally bent trunk and a curled and/or kinky tail, largely due to misregulated myotomal myod expression, implying perturbation of axial muscle differentiation in somites. Furthermore, the aberrant projection of spinal motor axons, which extended ventrally at the interface between the notochord and individual somites, was also observed in C4ST-1 morphants. These results suggest that 4-O-sulfated CS formed by C4ST-1 is essential for somitic muscle differentiation and motor axon guidance in zebrafish development.


Assuntos
Desenvolvimento Muscular/genética , Neurogênese/fisiologia , Sulfotransferases/fisiologia , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Animais , Sulfatos de Condroitina/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Imuno-Histoquímica , Hibridização In Situ , Isoenzimas/genética , Isoenzimas/metabolismo , Isoenzimas/fisiologia , Dados de Sequência Molecular , Neurogênese/genética , Ligação Proteica , Especificidade por Substrato , Sulfotransferases/genética , Sulfotransferases/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
13.
J Biol Chem ; 283(7): 4323-31, 2008 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-18056703

RESUMO

Neudesin is a secreted protein with neurotrophic activity in neurons and undifferentiated neural cells. We report here that neudesin is an extracellular heme-binding protein and that its neurotrophic activity is dependent on the binding of heme to its cytochrome b(5)-like heme/steroid-binding domain. At first, we found that at least a portion of the purified recombinant neudesin appeared to bind hemin because the purified neudesin solution was tinged with green and had a sharp absorbance peak at 402 nm. The addition of exogenous hemin extensively increased the amount of hemin-bound neudesin. In contrast, neudesinDeltaHBD, a mutant lacking the heme-binding domain, could not bind hemin. The neurotrophic activity of the recombinant neudesin that bound exogenous hemin (neudesin-hemin) was significantly greater than that of the recombinant neudesin in either primary cultured neurons or Neuro2a cells, suggesting that the activity of neudesin depends on hemin. The neurotrophic activity of neudesin was enhanced by the binding of Fe(III)-protoporphyrin IX, but neither Fe(II)-protoporphyrin IX nor protoporphyrin IX alone. The inhibition of endogenous neudesin by RNA interference significantly decreased cell survival in Neuro2a cells. This indicates that endogenous neudesin possibly contains hemin. The experiment with anti-neudesin antibody suggested that the endogenous neudesin detected in the culture medium of Neuro2a cells was associated with hemin because it was not retained on a heme-affinity column at all. Neudesin is the first extracellular heme-binding protein that shows signal transducing activity by itself. The present findings may shed new light on the function of extracellular heme-binding proteins.


Assuntos
Citocromos b5/metabolismo , Heme/metabolismo , Proteínas do Tecido Nervoso/fisiologia , Esteroides/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Western Blotting , Linhagem Celular Tumoral , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Primers do DNA , Camundongos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Ligação Proteica , RNA Interferente Pequeno , Homologia de Sequência de Aminoácidos
14.
Dev Biol ; 303(2): 527-35, 2007 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-17196583

RESUMO

We identified a novel secreted protein, fibin, in zebrafish, mice and humans. We inhibited its function in zebrafish embryos by injecting antisense fibin morpholino oligonucleotides. A knockdown of fibin function in zebrafish resulted in no pectoral fin bud initiation and abolished the expression of tbx5, which is involved in the specification of pectoral fin identification. The lack of pectoral fins in fibin-knockdown embryos was partially rescued by injection of fibin RNA. fibin was expressed in the lateral plate mesoderm of the presumptive pectoral fin bud regions. Its expression region was adjacent to that of tbx5. fibin expression temporally preceded tbx5 expression in presumptive pectoral fin bud regions, and not abolished in tbx5-knockdown presumptive fin bud regions. In contrast, fibin expression was abolished in retinoic acid signaling-inhibited or wnt2b-knockdown presumptive fin bud regions. These results indicate that fibin is a secreted signal essential for pectoral fin bud initiation in that it potentially acts downstream of retinoic acid and wnt signaling and is essential for tbx5 expression. The present findings have revealed a novel secreted lateral plate mesoderm signal essential for fin initiation in the lateral plate mesoderm.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Regulação da Expressão Gênica no Desenvolvimento , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mesoderma/metabolismo , Camundongos , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos Antissenso/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/antagonistas & inibidores , Proteínas de Peixe-Zebra/deficiência , Proteínas de Peixe-Zebra/genética
15.
EMBO Rep ; 7(6): 649-54, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16612391

RESUMO

Fibroblast growth factors (Fgfs) function as key secreted signalling molecules in many developmental events. The zebrafish is a powerful model system for the investigation of embryonic vertebrate haematopoiesis. Although the effects of Fgf signalling on haematopoiesis in vitro have been reported, the functions of Fgf signalling in haematopoiesis in vivo remain to be explained. We identified Fgf21 in zebrafish embryos. Fgf21-knockdown zebrafish embryos lacked erythroid and myeloid cells but not blood vessels and lymphoid cells. The knockdown embryos had haemangioblasts and haematopoietic stem cells. However, the knockdown embryos had significantly fewer myeloid and erythroid progenitor cells. In contrast, Fgf21 had no significant effect on cell proliferation and apoptosis in the intermediate cell mass. These results indicate that Fgf21 is a newly identified factor essential for the determination of myelo-erythroid progenitor cell fate in vivo.


Assuntos
Fatores de Crescimento de Fibroblastos/fisiologia , Hematopoese , Proteínas de Peixe-Zebra/fisiologia , Peixe-Zebra/embriologia , Animais , Cromossomos , Embrião não Mamífero/citologia , Embrião não Mamífero/fisiologia , Células Precursoras Eritroides/fisiologia , Fatores de Crescimento de Fibroblastos/genética , Células-Tronco Hematopoéticas/fisiologia , Modelos Biológicos , Oligonucleotídeos Antissenso/farmacologia , Filogenia , Proteínas de Peixe-Zebra/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...