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1.
Nature ; 626(8001): 1056-1065, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38122823

RESUMO

The temporal lobe of the human brain contains the entorhinal cortex (EC). This region of the brain is a highly interconnected integrative hub for sensory and spatial information; it also has a key role in episodic memory formation and is the main source of cortical hippocampal inputs1-4. The human EC continues to develop during childhood5, but neurogenesis and neuronal migration to the EC are widely considered to be complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions, with a large tangential stream persisting until the age of around one year and radial dispersal continuing until around two to three years of age. By contrast, we found no equivalent postnatal migration in rhesus macaques (Macaca mulatta). Immunostaining and single-nucleus RNA sequencing of ganglionic eminence germinal zones, the EC stream and the postnatal EC revealed that most migrating cells in the EC stream are derived from the caudal ganglionic eminence and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life, when children are actively interacting with their environment. The EC is one of the first regions of the brain to be affected in Alzheimer's disease, and previous work has linked cognitive decline to the loss of LAMP5+RELN+ cells6,7. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood.


Assuntos
Movimento Celular , Neurônios , Lobo Temporal , Animais , Pré-Escolar , Humanos , Lactente , Córtex Entorrinal/citologia , Córtex Entorrinal/fisiologia , Eminência Ganglionar/citologia , Interneurônios/citologia , Interneurônios/fisiologia , Macaca mulatta , Neurônios/citologia , Neurônios/fisiologia , Análise da Expressão Gênica de Célula Única , Lobo Temporal/citologia , Lobo Temporal/crescimento & desenvolvimento
2.
Development ; 149(4)2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35156680

RESUMO

The striatum is a central regulator of behavior and motor function through the actions of D1 and D2 medium-sized spiny neurons (MSNs), which arise from a common lateral ganglionic eminence (LGE) progenitor. The molecular mechanisms of cell fate specification of these two neuronal subtypes are incompletely understood. Here, we found that deletion of murine Meis2, which is highly expressed in the LGE and derivatives, led to a large reduction in striatal MSNs due to a block in their differentiation. Meis2 directly binds to the Zfp503 and Six3 promoters and is required for their expression and specification of D1 and D2 MSNs, respectively. Finally, Meis2 expression is regulated by Dlx1/2 at least partially through the enhancer hs599 in the LGE subventricular zone. Overall, our findings define a pathway in the LGE whereby Dlx1/2 drives expression of Meis2, which subsequently promotes the fate determination of striatal D1 and D2 MSNs via Zfp503 and Six3.


Assuntos
Corpo Estriado/metabolismo , Proteínas de Homeodomínio/metabolismo , Neurônios/metabolismo , Fatores de Transcrição/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Proteínas de Homeodomínio/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ventrículos Laterais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurogênese , Neurônios/citologia , Bulbo Olfatório/crescimento & desenvolvimento , Bulbo Olfatório/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Fatores de Transcrição/genética , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proteína Homeobox SIX3
3.
BMC Vet Res ; 20(1): 207, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760783

RESUMO

BACKGROUND: Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021. METHODS: All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community. RESULTS: Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05). CONCLUSIONS: US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.


Assuntos
Equinococose Hepática , Doenças dos Ovinos , Ultrassonografia , Animais , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/diagnóstico por imagem , Ovinos , China/epidemiologia , Ultrassonografia/veterinária , Equinococose Hepática/veterinária , Equinococose Hepática/epidemiologia , Equinococose Hepática/diagnóstico por imagem , Prevalência , Cães , Praziquantel/uso terapêutico , Anti-Helmínticos/uso terapêutico , Feminino
4.
Cereb Cortex ; 32(17): 3611-3632, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-34963132

RESUMO

The generation and differentiation of cortical projection neurons are extensively regulated by interactive programs of transcriptional factors. Here, we report the cooperative functions of transcription factors Bcl11a and Bcl11b in regulating the development of cortical projection neurons. Among the cells derived from the cortical neural stem cells, Bcl11a is expressed in the progenitors and the projection neurons, while Bcl11b expression is restricted to the projection neurons. Using conditional knockout mice, we show that deficiency of Bcl11a leads to reduced proliferation and precocious differentiation of cortical progenitor cells, which is exacerbated when Bcl11b is simultaneously deleted. Besides defective neuronal production, the differentiation of cortical projection neurons is blocked in the absence of both Bcl11a and Bcl11b: Expression of both pan-cortical and subtype-specific genes is reduced or absent; axonal projections to the thalamus, hindbrain, spinal cord, and contralateral cortical hemisphere are reduced or absent. Furthermore, neurogenesis-to-gliogenesis switch is accelerated in the Bcl11a-CKO and Bcl11a/b-DCKO mice. Bcl11a likely regulates neurogenesis through repressing the Nr2f1 expression. These results demonstrate that Bcl11a and Bcl11b jointly play critical roles in the generation and differentiation of cortical projection neurons and in controlling the timing of neurogenesis-to-gliogenesis switch.


Assuntos
Células-Tronco Neurais , Fatores de Transcrição , Animais , Diferenciação Celular/fisiologia , Camundongos , Camundongos Knockout , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Neurônios/fisiologia , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
5.
J Neurosci ; 41(12): 2554-2565, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762407

RESUMO

Adult hippocampal neurogenesis was originally discovered in rodents. Subsequent studies identified the adult neural stem cells and found important links between adult neurogenesis and plasticity, behavior, and disease. However, whether new neurons are produced in the human dentate gyrus (DG) during healthy aging is still debated. We and others readily observe proliferating neural progenitors in the infant hippocampus near immature cells expressing doublecortin (DCX), but the number of such cells decreases in children and few, if any, are present in adults. Recent investigations using dual antigen retrieval find many cells stained by DCX antibodies in adult human DG. This has been interpreted as evidence for high rates of adult neurogenesis, even at older ages. However, most of these DCX-labeled cells have mature morphology. Furthermore, studies in the adult human DG have not found a germinal region containing dividing progenitor cells. In this Dual Perspectives article, we show that dual antigen retrieval is not required for the detection of DCX in multiple human brain regions of infants or adults. We review prior studies and present new data showing that DCX is not uniquely expressed by newly born neurons: DCX is present in adult amygdala, entorhinal and parahippocampal cortex neurons despite being absent in the neighboring DG. Analysis of available RNA-sequencing datasets supports the view that DG neurogenesis is rare or absent in the adult human brain. To resolve the conflicting interpretations in humans, it is necessary to identify and visualize dividing neuronal precursors or develop new methods to evaluate the age of a neuron at the single-cell level.


Assuntos
Hipocampo/citologia , Hipocampo/fisiologia , Neurogênese/fisiologia , Neurônios/fisiologia , Adulto , Diferenciação Celular/fisiologia , Criança , Humanos , Plasticidade Neuronal/fisiologia
6.
Development ; 145(14)2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-29967281

RESUMO

Dopamine receptor DRD1-expressing medium spiny neurons (D1 MSNs) and dopamine receptor DRD2-expressing medium spiny neurons (D2 MSNs) are the principal projection neurons in the striatum, which is divided into dorsal striatum (caudate nucleus and putamen) and ventral striatum (nucleus accumbens and olfactory tubercle). Progenitors of these neurons arise in the lateral ganglionic eminence (LGE). Using conditional deletion, we show that mice lacking the transcription factor genes Sp8 and Sp9 lose virtually all D2 MSNs as a result of reduced neurogenesis in the LGE, whereas D1 MSNs are largely unaffected. SP8 and SP9 together drive expression of the transcription factor Six3 in a spatially restricted domain of the LGE subventricular zone. Conditional deletion of Six3 also prevents the formation of most D2 MSNs, phenocopying the Sp8/9 mutants. Finally, ChIP-Seq reveals that SP9 directly binds to the promoter and a putative enhancer of Six3 Thus, this study defines components of a transcription pathway in a regionally restricted LGE progenitor domain that selectively drives the generation of D2 MSNs.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas do Olho/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Células-Tronco Neurais/metabolismo , Neurônios/metabolismo , Fatores de Transcrição/metabolismo , Animais , Proteínas de Ligação a DNA/genética , Proteínas do Olho/genética , Proteínas de Homeodomínio/genética , Camundongos , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Células-Tronco Neurais/citologia , Neurônios/citologia , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Fatores de Transcrição/genética , Proteína Homeobox SIX3
7.
Opt Express ; 28(19): 28085-28100, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32988087

RESUMO

The three-channel spectral sensitivity of a trichromatic camera represents the characteristics of system color space. It is a mapping bridge from the spectral information of a scene to the response value of a camera. In this paper, we propose an estimation method for three-channel spectral sensitivity of a trichromatic camera. It includes calibration experiment by orthogonal test design and the data processing by window filtering. The calibration experiment was first designed by an orthogonal table of the 9-level and 3-factor. A rough estimation model of spectral sensitivity is established on the data pairs of the system input and output in calibration experiments. The data of rough estimation is then modulated by two window filters on frequency and spatial domain. The Luther-Ives condition and the smoothness condition are introduced to design the window, and help to achieve the optimal estimation of the system spectral sensitivity. Finally, the proposed method is verified by some comparison experiments. The results show that the estimated spectral sensitivity is basically consistent with the measured results of the monochromator experiments, the relative full-scale errors of the RGB three-channel is obviously lower than the Wiener filtering method and the Fourier band-limitedness method. The proposed method can estimate the spectral sensitivity of the trichromatic digital camera very well, which is of great significance for the colorimetric characterization and evaluation of imaging systems.

8.
Cereb Cortex ; 29(6): 2653-2667, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29878134

RESUMO

Immature neurons generated by the subpallial MGE tangentially migrate to the cortex where they become parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons. Here, we show that the Sp9 transcription factor controls the development of MGE-derived cortical interneurons. SP9 is expressed in the MGE subventricular zone and in MGE-derived migrating interneurons. Sp9 null and conditional mutant mice have approximately 50% reduction of MGE-derived cortical interneurons, an ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased ratio of SST+/PV+ cortical interneurons. RNA-Seq and SP9 ChIP-Seq reveal that SP9 regulates MGE-derived cortical interneuron development through controlling the expression of key transcription factors Arx, Lhx6, Lhx8, Nkx2-1, and Zeb2 involved in interneuron development, as well as genes implicated in regulating interneuron migration Ackr3, Epha3, and St18. Thus, Sp9 has a central transcriptional role in MGE-derived cortical interneuron development.


Assuntos
Córtex Cerebral/citologia , Interneurônios/citologia , Eminência Mediana/embriologia , Neurogênese/fisiologia , Proteínas de Ligação a RNA/metabolismo , Animais , Movimento Celular/fisiologia , Córtex Cerebral/embriologia , Interneurônios/metabolismo , Eminência Mediana/citologia , Camundongos , Fatores de Transcrição/metabolismo
9.
Cereb Cortex ; 29(11): 4831-4849, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30796806

RESUMO

Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2F/- mice), GSX2+ and ASCL1+ neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1, and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Interneurônios/metabolismo , Células-Tronco Neurais/metabolismo , Bulbo Olfatório/metabolismo , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neocórtex/embriologia , Neocórtex/metabolismo , Bulbo Olfatório/embriologia
10.
Cereb Cortex ; 28(9): 3278-3294, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28981617

RESUMO

Neural stem cells in the postnatal telencephalic ventricular-subventricular zone (V-SVZ) generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) into the olfactory bulb (OB). The Sp8 and Sp9 transcription factors are expressed in neuroblasts, as well as in the immature and mature interneurons in the V-SVZ-RMS-OB system. Here we show that Sp8 and Sp9 coordinately regulate OB interneuron development: although Sp9 null mutants show no major OB interneuron defect, conditional deletion of both Sp8 and Sp9 resulted in a much more severe reduction of OB interneuron number than that observed in the Sp8 conditional mutant mice, due to defects in neuronal differentiation, tangential and radial migration, and increased cell death in the V-SVZ-RMS-OB system. RNA-Seq and RNA in situ hybridization reveal that, in Sp8/Sp9 double mutant mice, but not in Sp8 or Sp9 single mutant mice, newly born neuroblasts in the V-SVZ-RMS-OB system fail to express Prokr2 and Tshz1 expression, genes with known roles in promoting OB interneuron differentiation and migration, and that are involved in human Kallmann syndrome.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Interneurônios/metabolismo , Neurogênese/fisiologia , Bulbo Olfatório/crescimento & desenvolvimento , Bulbo Olfatório/fisiologia , Fatores de Transcrição/metabolismo , Animais , Interneurônios/citologia , Camundongos , Camundongos Knockout , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo
11.
Korean J Parasitol ; 57(2): 153-159, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31104407

RESUMO

Echinococcus granulosus is an important zoonotic parasite globally causing cystic echinococcosis (CE) in humans and animals. In this study, prevalence of CE and variation of cox1 gene sequence were analyzed with isolates E. granulosus collected from different areas in northern Xinjiang, China. The survey showed that 3.5% of sheep and 4.1% of cattle were infected with CE. Fragment of cox1 was amplified from all the positive sheep and cattle samples by PCR. In addition, 26 positive samples across the 4 areas were included. The isolates were all E. granulosus sensu stricto (s.s.) containing 15 haplotypes (Hap1-15), and clustered into 2 genotypes, G1 (90.1%, 91/101) and G3 (9.9%, 10/101). Hap1 was the most common haplotype (48.5%, 49/101). Hap9 were found in humans samples, indicating that sheep and cattle reservoir human CE. It is indicate that E. granulosus may impact on control of CE in livestock and humans in the region.


Assuntos
Doenças dos Bovinos/epidemiologia , Equinococose/epidemiologia , Equinococose/veterinária , Echinococcus granulosus/genética , Echinococcus granulosus/isolamento & purificação , Doenças dos Ovinos/epidemiologia , Animais , Bovinos , Doenças dos Bovinos/parasitologia , China/epidemiologia , Análise por Conglomerados , Equinococose/parasitologia , Echinococcus granulosus/classificação , Complexo IV da Cadeia de Transporte de Elétrons/genética , Genótipo , Humanos , Epidemiologia Molecular , Prevalência , Ovinos , Doenças dos Ovinos/parasitologia
12.
J Neurosci ; 34(33): 10906-23, 2014 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-25122892

RESUMO

In adult rodent and monkey brains, newly born neurons in the subventricular zone (SVZ) in the wall of the lateral ventricle migrate into the olfactory bulb (OB) via the rostral migratory stream (RMS). A recent study reported that interneurons are constantly generating in the adult human striatum from the SVZ. In contrast, by taking advantage of the continuous expression of Sp8 from the neuroblast stage through differentiation into mature interneurons, we found that the adult human SVZ does not generate new interneurons for the striatum. In the adult human SVZ and RMS, very few neuroblasts were observed, and most of them expressed the transcription factor Sp8. Neuroblasts in the adult rhesus monkey SVZ-RMS-OB pathway also expressed Sp8. In addition, we observed that Sp8 was expressed by most adult human and monkey OB interneurons. However, very few Sp8+ cells were in the adult human striatum. This suggests that neuroblasts in the adult human SVZ and RMS are likely destined for the OB, but not for the striatum. BrdU-labeling results also revealed few if any newly born neurons in the adult rhesus monkey striatum. Finally, on the basis of transcription factor expression, we provide strong evidence that the vast majority of interneurons in the human and monkey striatum are generated from the medial ganglionic eminence during embryonic developmental stages, as they are in rodents. We conclude that, although a small number of neuroblasts exist in the adult human SVZ, they do not migrate into the striatum and become mature striatal interneurons.


Assuntos
Corpo Estriado/citologia , Interneurônios/citologia , Ventrículos Laterais/citologia , Eminência Mediana/citologia , Neurogênese/fisiologia , Animais , Linhagem da Célula/fisiologia , Movimento Celular/fisiologia , Feminino , Humanos , Macaca mulatta , Masculino
13.
BMC Genomics ; 15: 736, 2014 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-25168356

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are important post-transcriptional regulators which control growth and development in eukaryotes. The cestode Echinococcus granulosus has a complex life-cycle involving different development stages but the mechanisms underpinning this development, including the involvement of miRNAs, remain unknown. RESULTS: Using Illumina next generation sequencing technology, we sequenced at the genome-wide level three small RNA populations from the adult, protoscolex and cyst membrane of E. granulosus. A total of 94 pre-miRNA candidates (coding 91 mature miRNAs and 39 miRNA stars) were in silico predicted. Through comparison of expression profiles, we found 42 mature miRNAs and 23 miRNA stars expressed with different patterns in the three life stages examined. Furthermore, considering both the previously reported and newly predicted miRNAs, 25 conserved miRNAs families were identified in the E. granulosus genome. Comparing the presence or absence of these miRNA families with the free-living Schmidtea mediterranea, we found 13 conserved miRNAs are lost in E. granulosus, most of which are tissue-specific and involved in the development of ciliated cells, the gut and sensory organs. Finally, GO enrichment analysis of the differentially expressed miRNAs and their potential targets indicated that they may be involved in bi-directional development, nutrient metabolism and nervous system development in E. granulosus. CONCLUSIONS: This study has, for the first time, provided a comprehensive description of the different expression patterns of miRNAs in three distinct life cycle stages of E. granulosus. The analysis supports earlier suggestions that the loss of miRNAs in the Platyhelminths might be related to morphological simplification. These results may help in the exploration of the mechanism of interaction between this parasitic worm and its definitive and intermediate hosts, providing information that can be used to develop new interventions and therapeutics for the control of cystic echinococcosis.


Assuntos
Echinococcus granulosus/genética , MicroRNAs/genética , RNA de Helmintos/genética , Animais , Sequência de Bases , Sequência Conservada , Echinococcus granulosus/metabolismo , Genoma Helmíntico , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/metabolismo , Anotação de Sequência Molecular , Dados de Sequência Molecular , Especificidade de Órgãos , Interferência de RNA , RNA de Helmintos/metabolismo , Análise de Sequência de RNA , Transcriptoma
14.
Protein Cell ; 15(1): 21-35, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37300483

RESUMO

The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.


Assuntos
Células Ependimogliais , Proteínas Hedgehog , Animais , Camundongos , Humanos , Células Ependimogliais/metabolismo , Proteínas Hedgehog/metabolismo , Furões/metabolismo , Córtex Cerebral , Neurogênese , Mamíferos/metabolismo , Neuroglia/metabolismo , Proteína Morfogenética Óssea 7/metabolismo
15.
Pathogens ; 12(1)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36678482

RESUMO

Cystic echinococcosis (CE), caused by the metacestode Echinococcus granulosus sensu stricto (s.s.), is an important zoonotic parasite, endemic in the Altai region of China. It is a serious human health risk and causes livestock losses. To evaluate the prevalence, genetic variation, and population structure of CE, 2898 sheep and 703 cattle were examined from October 2019 to mid-February 2020 in the Altai region (Altai, Habahe, Fuhai, and Buerjin). Sheep had an infection rate of 4.52% (131/2898) and cattle had an infection rate of 4.84% (34/703). In total, 180 cyst isolates were obtained, including 131 sheep, 34 cattle, and 15 from CE human patients. The cysts were investigated using mitochondrial cytochrome C oxidase subunit 1 (cox1). Polymerase Chain Reaction (PCR) results showed that, among the two genotypes of E. granulosus s.s., there were 22 different haplotypes (Haps). Phylogenetic analysis and parsimony network indicated that seventeen (77.27%) Haps belonged to the sheep strain (G1 genotype) and five Haps (22.73%) belonged to the buffalo strain (G3 genotype). Hap3 was the most common haplotype (65.00%, 112/180), which belongs to the G1 genotype. Hap18−Hap22 were found in human samples, indicating that sheep and cattle reservoirs of human CE. Molecular diversity indices revealed the high levels of haplotype diversity and relatively low levels of nucleotide diversity. Tajima's D and Fu's Fs tests displayed that the Altai population had a significant deviation from neutrality. Based on pairwise fixation index (Fst) values, a low level of genetic differentiation was found between the populations of E. granulosus s.s. isolated from different regions. The present survey findings represent an epidemiological survey of CE in the Altai region where there were two genotypes simultaneously and will provide more information on the genetic structure of E. granulosus s.s. within this region.

16.
Microbiol Spectr ; 11(3): e0070223, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37042768

RESUMO

Parasitic flatworms infect diverse vertebrates and are major threats to animal and even human health; however, little is known about the virome of these lower life forms. Using viral metagenomic sequencing, we characterized the virome of the parasitic flatworms collected from major domestic animals, including Dicrocoelium lanceatum and Taenia hydatigena, Echinococcus granulosus sensu stricto and Echinococcus multilocularis. Seven and three different viruses were discovered from D. lanceatum and T. hydatigena, respectively, and no viral sequences were found in adult tapeworms and protoscoleces of E. granulosus sensu stricto and E. multilocularis. Two out of the five parasitic flatworm species carry viruses, showing a host specificity of these viruses. These viruses belong to the Parvoviridae, Circoviridae, unclassified circular, Rep-encoding single-stranded (CRESS) DNA virus, Rhabdoviridae, Endornaviridae, and unclassified RNA viruses. The presence of multiple highly divergent RNA viruses, especially those that cluster with viruses found in marine animals, implies a deep evolutionary history of parasite-associated viruses. In addition, we found viruses with high identity to common pathogens in dogs, including canine circovirus and canine parvovirus 2. The presence of these viruses in the parasites implies that they may infect parasitic flatworms but does not completely exclude the possibility of contamination from host intestinal contents. Furthermore, we demonstrated that certain viruses, such as CRESS DNA virus may integrate into the genome of their host. Our results expand the knowledge of viral diversity in parasites of important domestic animals, highlighting the need for further investigations of their prevalence among other parasites of key animals. IMPORTANCE Characterizing the virome of parasites is important for unveiling the viral diversity, evolution, and ecology and will help to understand the "Russian doll" pattern among viruses, parasites, and host animals. Our data indicate that diverse viruses are present in specific parasitic flatworms, including viruses that may have an ancient evolutionary history and viruses currently circulating in parasite-infected host animals. These data also raise the question of whether parasitic flatworms acquire and/or carry some viruses that may have transmission potential to animals. In addition, through the study of virus-parasite-host interactions, including the influence of viral infection on the life cycle of the parasite, as well as its fitness and pathogenicity to the host, we could find new strategies to prevent and control parasitic diseases.


Assuntos
Platelmintos , Vírus de RNA , Vírus , Adulto , Animais , Cães , Humanos , Animais Domésticos , Filogenia , Viroma , Vírus/genética , Metagenoma
17.
Cell Death Discov ; 8(1): 301, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35773249

RESUMO

The striatum is the main input structure of the basal ganglia, receiving information from the cortex and the thalamus and consisting of D1- and D2- medium spiny neurons (MSNs). D1-MSNs and D2-MSNs are essential for motor control and cognitive behaviors and have implications in Parkinson's Disease. In the present study, we demonstrated that Sp9-positive progenitors produced both D1-MSNs and D2-MSNs and that Sp9 expression was rapidly downregulated in postmitotic D1-MSNs. Furthermore, we found that sustained Sp9 expression in lateral ganglionic eminence (LGE) progenitor cells and their descendants led to promoting D2-MSN identity and repressing D1-MSN identity during striatal development. As a result, sustained Sp9 expression resulted in an imbalance between D1-MSNs and D2-MSNs in the mouse striatum. In addition, the fate-changed D2-like MSNs survived normally in adulthood. Taken together, our findings supported that Sp9 was sufficient to promote D2-MSN identity and repress D1-MSN identity, and Sp9 was a negative regulator of D1-MSN fate.

18.
Front Cell Dev Biol ; 10: 948331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081908

RESUMO

The striatum is primarily composed of two types of medium spiny neurons (MSNs) expressing either D1- or D2-type dopamine receptors. However, the fate determination of these two types of neurons is not fully understood. Here, we found that D1 MSNs undergo fate switching to D2 MSNs in the absence of Zfp503. Furthermore, scRNA-seq revealed that the transcription factor Zfp503 affects the differentiation of these progenitor cells in the lateral ganglionic eminence (LGE). More importantly, we found that the transcription factors Sp8/9, which are required for the differentiation of D2 MSNs, are repressed by Zfp503. Finally, sustained Zfp503 expression in LGE progenitor cells promoted the D1 MSN identity and repressed the D2 MSN identity. Overall, our findings indicated that Zfp503 promotes the D1 MSN identity and represses the D2 MSN identity by regulating Sp8/9 expression during striatal MSN development.

19.
Vet Parasitol ; 297: 109069, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32156436

RESUMO

Trichinellosis caused by Trichinella spiralis (T. spiralis) is an important public health problem. DNase II is an acidic endonuclease that catalyzes the degradation of DNA into oligonucleotides. DNase II-7 has been detected at the adult stage of T. spiralis and has been examined in excretory/secretory products. Previous studies have indicated that the DNase II-7 recombinant protein has a high rate of protection against T. spiralis infection in mice. In the present study, the protective effect of DNase II-7 recombinant protein against T. spiralis infection in Large White pigs was further explored. The humoral and cellular immune responses to the DNase II-7 recombinant protein were evaluated, including the dynamic trends of specific IgG, IgG1, IgG2a and IgM antibodies levels, as well as the levels of Th1 (IFN-γ and IL-2) and Th2 (IL-10 and IL-4) cytokines in serum. Our results showed that a Th1 dominated Th1/Th2 mixed immune response was induced by the DNase II-7 recombinant protein for all the time or a short period after vaccination. And the DNase II-7 recombinant protein induced partial protection against T. spiralis infection in pigs, compared to the control group. Our results showed that the DNase II-7 recombinant protein group displayed a 45.7 % reduction in the muscle larvae burden five weeks after being challenged. This study suggested that DNaseII-7 recombinant protein could be used as a potential candidate vaccine against T. spiralis infection in pigs.


Assuntos
Doenças dos Roedores , Doenças dos Suínos , Trichinella spiralis , Triquinelose , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes , Suínos , Doenças dos Suínos/prevenção & controle , Triquinelose/prevenção & controle , Triquinelose/veterinária , Vacinação/veterinária
20.
Cell Death Dis ; 12(3): 262, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712552

RESUMO

The striatum is structurally highly diverse, and its organ functionality critically depends on normal embryonic development. Although several studies have been conducted on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive transcriptome profile that allows us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington's disease (HD). Furthermore, we applied an integrative transcriptomic profiling approach based on machine learning to systematically map a global landscape of 277 transcription factor (TF) networks. Most of these TF networks are linked to biological processes, and some unannotated genes provide information about the corresponding mechanisms. For example, we found that the Meis2 and Six3 were crucial for the survival of striatal neurons, which were verified using conditional knockout (CKO) mice. Finally, we used RNA-Seq to speculate their downstream targets.


Assuntos
Apoptose , Corpo Estriado/patologia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Doença de Huntington/genética , Doença de Huntington/patologia , Fatores de Transcrição/genética , Transcriptoma , Animais , Estudos de Casos e Controles , Bases de Dados Genéticas , Proteínas do Olho/genética , Regulação da Expressão Gênica no Desenvolvimento , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Humanos , Aprendizado de Máquina , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Fenótipo , RNA-Seq , Proteína Homeobox SIX3
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