Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Mol Psychiatry ; 17(4): 451-66, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22124272

RESUMO

Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia, autism spectrum disorder and bipolar disorder. 14-3-3ζ-deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippocampus that are underpinned by aberrant neuronal migration. Significantly, 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network.


Assuntos
Proteínas 14-3-3/fisiologia , Encéfalo/crescimento & desenvolvimento , Predisposição Genética para Doença/genética , Hipocampo/crescimento & desenvolvimento , Neurogênese/fisiologia , Esquizofrenia/genética , Proteínas 14-3-3/genética , Animais , Encéfalo/metabolismo , Movimento Celular/genética , Movimento Celular/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/fisiologia , Neurogênese/genética , Neurônios/metabolismo , Neurônios/fisiologia , Reconhecimento Psicológico/fisiologia , Filtro Sensorial/fisiologia
2.
Exp Cell Res ; 308(1): 166-76, 2005 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-15916758

RESUMO

Stem and progenitor cells have been identified in many adult tissues including bone marrow, the central nervous system, and skin. While there is direct evidence to indicate the activity of a progenitor cell population in the pituitary gland, this putative subpopulation has not yet been identified. Herein we describe the isolation and characterization of a novel clonogenic cell type in the adult murine pituitary, which we have termed Pituitary Colony-Forming Cells (PCFCs). PCFCs constitute 0.2% of pituitary cells, and generate heterogeneous colonies from single cells. PCFCs exhibit variable proliferative potential, and may exceed 11 population doublings in 14 days. Enrichment of PCFCs to 61.5-fold with 100% recovery can be obtained through the active uptake of the fluorescent dipeptide, beta-Ala-Lys-Nepsilon-AMCA. PCFCs are mostly contained within the large, agranular subpopulation of AMCA+ cells, and constitute 28% of this fraction, corresponding to 140.5-fold enrichment. Interestingly, the AMCA+ population contains rare cells that are GH+ or PRL+. GH+ cells were also identified in PCFC single cell colonies, suggesting that PCFCs have the potential to differentiate into GH+ cells. Together, these data show that the pituitary contains a rare clonogenic population which may correspond to the somatotrope/lactotrope progenitors suggested by previous experiments.


Assuntos
Hipófise/citologia , Células-Tronco/citologia , Animais , Biomarcadores/análise , Contagem de Células , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Cumarínicos/farmacocinética , Cumarínicos/farmacologia , Feminino , Camundongos , Oligopeptídeos/farmacocinética , Oligopeptídeos/farmacologia , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo
3.
Gene Expr Patterns ; 5(3): 305-11, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15661635

RESUMO

During the development of the anterior pituitary gland, five distinct hormone-producing cell types emerge in a spatially and temporally regulated pattern from an invagination of oral ectoderm termed Rathke's Pouch. Evidence from mouse knockout and ectopic expression studies indicates that 12.5 days post coitum (dpc) to 14.5 dpc is a critical period for the expansion of the progenitor cell pool and the determination of most hormone-secreting cell types. While signaling proteins and transcription factors have been identified as having key roles in pituitary cell differentiation, little is known about the identity and function of proteins that mediate signal transduction in progenitor cells. To identify genes that are enriched in the embryonic pituitary gland, we compared gene expression in 14.5 dpc pituitary and 14.5 dpc embryo minus pituitary tissues using the NIA 15K microarray. Analysis of the data using the R program revealed that the Regulator of G Protein Signaling 2 (Rgs2) gene was 3.9-fold more abundant in the 14.5 dpc pituitary. In situ hybridisation confirmed this finding, and showed that Rgs2 expression in midline tissues was restricted to the pituitary and discrete regions of the nervous system. Within the pituitary, Rgs2 was expressed in undifferentiated cells, and was downregulated at the completion of the hormone cell differentiation. To investigate Rgs2 function in the pituitary, we examined hormone cell differentiation in Rgs2 null neonate mice. Pituitary cell differentiation and morphology appeared normal in the Rgs2 mutant animals, suggesting that other Rgs family members with similar activities may be present in the developing pituitary.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Hipófise/embriologia , Proteínas RGS/biossíntese , Animais , Animais Recém-Nascidos , Diferenciação Celular , Regulação para Baixo , Proteínas de Homeodomínio/biossíntese , Hibridização In Situ , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Hipófise/citologia , Hipófise/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
4.
J Med Genet ; 41(9): 669-78, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15342697

RESUMO

INTRODUCTION: Array comparative genomic hybridisation (array CGH) is a powerful method that detects alteration of gene copy number with greater resolution and efficiency than traditional methods. However, its ability to detect disease causing duplications in constitutional genomic DNA has not been shown. We developed an array CGH assay for X linked hypopituitarism, which is associated with duplication of Xq26-q27. METHODS: We generated custom BAC/PAC arrays that spanned the 7.3 Mb critical region at Xq26.1-q27.3, and used them to search for duplications in three previously uncharacterised families with X linked hypopituitarism. RESULTS: Validation experiments clearly identified Xq26-q27 duplications that we had previously mapped by fluorescence in situ hybridisation. Array CGH analysis of novel XH families identified three different Xq26-q27 duplications, which together refine the critical region to a 3.9 Mb interval at Xq27.2-q27.3. Expression analysis of six orthologous mouse genes from this region revealed that the transcription factor Sox3 is expressed at 11.5 and 12.5 days after conception in the infundibulum of the developing pituitary and the presumptive hypothalamus. DISCUSSION: Array CGH is a robust and sensitive method for identifying X chromosome duplications. The existence of different, overlapping Xq duplications in five kindreds indicates that X linked hypopituitarism is caused by increased gene dosage. Interestingly, all X linked hypopituitarism duplications contain SOX3. As mutation of this gene in human beings and mice results in hypopituitarism, we hypothesise that increased dosage of Sox3 causes perturbation of pituitary and hypothalamic development and may be the causative mechanism for X linked hypopituitarism.


Assuntos
Cromossomos Humanos X/genética , Proteínas de Ligação a DNA/genética , Duplicação Gênica , Genes Duplicados/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas de Grupo de Alta Mobilidade/genética , Hipopituitarismo/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Ligação Genética/genética , Genoma Humano , Humanos , Hipotálamo/embriologia , Hipotálamo/metabolismo , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Camundongos , Hibridização de Ácido Nucleico , Linhagem , Hipófise/embriologia , Hipófise/metabolismo , Reprodutibilidade dos Testes , Fatores de Transcrição SOXB1
5.
Dev Biol ; 265(2): 329-40, 2004 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-14732396

RESUMO

Normal development of the pituitary gland requires coordination between the maintenance of a progenitor cell pool and the selection of progenitor cells for differentiation. As Notch signaling controls progenitor cell differentiation in many embryonic tissues, we investigated the involvement of this important developmental pathway in the embryonic pituitary. We report that expression of Notch signaling genes is spatially and temporally regulated in pituitary embryogenesis and implicate Notch2 in the differentiation of several cell lineages. Notch2, Notch3, and Dll1 are initially expressed by most cells within the pituitary primordium and become restricted to a subset of the progenitor cell pool as differentiated pituitary cells begin to appear. Mutations in the transcription factor Prop1 interfere with pituitary growth and cell specification, although the mechanism is unknown. Notch2 expression is nearly absent in the developing pituitaries of Prop1 mutant mice, but unaltered in some other panhypopituitary mutants, revealing that Prop1 is directly or indirectly required for normal Notch2 expression. Transgenic overexpression of Prop1 is not sufficient for enhancement of endogenous Notch2 expression, indicating that there are multiple inputs into this pathway. Dll3 is expressed only in the presumptive corticotrope and melanotrope cells. Analysis of Dll3 null mutants indicates that Dll3 is not required for specification of these two cell types, although there may be functional overlap with Dll1. The spatial and temporal expression patterns of Notch signaling genes in the pituitary suggest overlapping roles in pituitary growth and cell specification.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas de Homeodomínio/metabolismo , Proteínas de Membrana/metabolismo , Hipófise/embriologia , Transdução de Sinais/fisiologia , Animais , Diferenciação Celular/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Proteínas de Homeodomínio/genética , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Hipófise/metabolismo , RNA Mensageiro/metabolismo , Receptores Notch
6.
Dev Biol ; 229(2): 503-16, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11150245

RESUMO

In situ hybridization revealed that GDNF mRNA in the mid- and hindgut mesenchyme of embryonic mice was minimal at E10.5 but was rapidly elevated at all gut regions after E11, but with a slight delay (0.5 days) in the hindgut. GDNF mRNA expression was minimal in the mesentery and in the pharyngeal and pelvic mesenchyme adjacent to the gut. To examine the effect of GDNF on enteric neural crest-derived cells, segments of E11.5 mouse hindgut containing crest-derived cells only at the rostral ends were attached to filter paper supports and grown in catenary organ culture. With GDNF (100 ng/ml) in the culture medium, threefold fewer neurons developed in the gut explants and fivefold more neurons were present on the filter paper outside the gut explants, compared to controls. Thus, in controls, crest-derived cells colonized the entire explant and differentiated into neurons, whereas in the presence of exogenous GDNF, most crest-derived cells migrated out of the gut explant. This is consistent with GDNF acting as a chemoattractant. To test this idea, explants of esophagus, midgut, superior cervical ganglia, paravertebral sympathetic chain ganglia, or dorsal root ganglia from E11.5-E12.5 mice were grown on collagen gels with a GDNF-impregnated agarose bead on one side and a control bead on the opposite side. Migrating neural cells and neurites from the esophagus and midgut accumulated around the GDNF-impregnated beads, but neural cells in other tissues showed little or no chemotactic response to GDNF, although all showed GDNF-receptor (Ret and GFRalpha1) immunoreactivity. We conclude that GDNF may promote the migration of crest cells throughout the gastrointestinal tract, prevent them from straying out of the gut (into the mesentery and pharyngeal and pelvic tissues), and promote directed axon outgrowth.


Assuntos
Sistema Nervoso Entérico/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Intestinos/embriologia , Fatores de Crescimento Neural/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/farmacologia , Neurônios/fisiologia , Animais , Ceco/embriologia , Ceco/inervação , Divisão Celular/efeitos dos fármacos , Desenvolvimento Embrionário e Fetal , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Intestinos/inervação , Camundongos , Fatores de Crescimento Neural/farmacologia , Fatores de Crescimento Neural/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios/citologia , Neurônios/efeitos dos fármacos , Técnicas de Cultura de Órgãos , RNA Mensageiro/genética , Transcrição Gênica
7.
Hum Mol Genet ; 10(1): 39-45, 2001 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11136712

RESUMO

We have previously shown that familial septo-optic dysplasia (SOD), a syndromic form of congenital hypopituitarism involving optic nerve hypoplasia and agenesis of midline brain structures, is associated with homozygosity for an inactivating mutation in the homeobox gene HESX1/Hesx1 in man and mouse. However, as most SOD/congenital hypopituitarism occurs sporadically, the possible contribution of HESX1 mutations to the aetiology of these cases is presently unclear. Interestingly, a small proportion of mice heterozygous for the Hesx1 null allele show a milder SOD phenocopy, implying that heterozygous mutations in human HESX1 could underlie some cases of congenital pituitary hypoplasia with or without midline defects. Accordingly, we have now scanned for HESX1 mutations in 228 patients with a broad spectrum of congenital pituitary defects, ranging in severity from isolated growth hormone deficiency to SOD with panhypopituitarism. Three different heterozygous missense mutations were detected in individuals with relatively mild pituitary hypoplasia or SOD, which display incomplete penetrance and variable phenotype amongst heterozygous family members. Gel shift analysis of the HESX1-S170L mutant protein, which is encoded by the C509T mutated allele, indicated that a significant reduction in relative DNA binding activity results from this mutation. Segregation analysis of a haplotype spanning 6.1 cM, which contains the HESX1 locus, indicated that only one HESX1 mutation was present in the families containing the C509T and A541G mutations. These results demonstrate that some sporadic cases of the more common mild forms of pituitary hypoplasia have a genetic basis, resulting from heterozygous mutation of the HESX1 gene.


Assuntos
Proteínas de Homeodomínio/genética , Mutação , Nervo Óptico/anormalidades , Hipófise/anormalidades , Alelos , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Criança , Cromossomos Artificiais de Levedura , DNA/metabolismo , Saúde da Família , Feminino , Haplótipos , Heterozigoto , Humanos , Lactente , Masculino , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Proteínas Repressoras , Fatores de Transcrição HES-1
8.
Horm Res ; 53 Suppl 1: 26-33, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10895039

RESUMO

Septo-optic dysplasia (SOD) is a highly variable condition characterized by midline neurological abnormalities associated with pituitary hypoplasia and optic nerve hypoplasia. The aetiology is unknown. Mutant mice, in which a novel homeobox gene, Hesx1, has been disrupted, exhibit a phenotype that resembles the phenotype of SOD. We therefore wished to explore the possibility that this gene is implicated in SOD. We cloned and sequenced the human homologue HESX1 and screened for mutations in affected individuals using single-stranded conformational polymorphism analysis, followed by cloning and sequencing of any exons which showed a band shift. Two siblings with SOD were homozygous for an Arg53Cys missense mutation within the HESX1 homeodomain, leading to a loss of in vitro DNA binding. Subsequently, we have identified heterozygous mutations in HESX1 that are associated with milder pituitary phenotypes. Our studies indicate a vital role for Hesx1/HESX1 in forebrain and pituitary development in mouse and man, and hence in some cases of SOD.


Assuntos
Genes Homeobox , Proteínas de Homeodomínio/genética , Mutação , Nervo Óptico/anormalidades , Septo Pelúcido/anormalidades , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Humanos , Camundongos , Biologia Molecular , Linhagem , Adeno-Hipófise/embriologia , Proteínas Repressoras , Fatores de Transcrição HES-1
9.
J Clin Endocrinol Metab ; 85(12): 4556-61, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11134108

RESUMO

Incomplete differentiation of the anterior pituitary (AP) hormone-secreting cells can result in combined pituitary hormone deficiency (CPHD), in which patients display deficiencies in GH and at least one other AP hormone. The majority of familial CPHD cases are due to mutations in the pituitary transcription factor PROP1 (Prophet of Pit1). We have scanned for PROP1 mutations in a large consanguineous Indian CPHD pedigree and identified a novel 13-bp deletion in exon 2 that is predicted to generate a null allele. Assessment of GH, TSH, gonadotropin, and PRL levels in homozygous affected individuals indicated impaired production of these hormones by the AP. Interestingly, two of the affected subjects also displayed cortisol deficiency, which was progressive in one of these patients. This phenotypic feature is not normally associated with CPHD resulting from PROP1 mutation. These data show that PROP1 mutations can result in panhypopituitarism, the most severe form of AP deficiency, in which the production of all hormones is compromised and support a role for PROP1 in the maintenance and/or differentiation of all five hormone-secreting cell types. From a clinical perspective, these data indicate that the presence of an impaired pituitary-adrenal axis in CPHD patients does not exclude the possibility of an underlying PROP1 gene defect.


Assuntos
Hormônio Adrenocorticotrópico/deficiência , Deleção de Genes , Proteínas de Homeodomínio/genética , Hipopituitarismo/genética , Mutação/genética , Hormônios Hipofisários/deficiência , Fatores de Transcrição/genética , Adolescente , Adulto , Sequência de Bases , Criança , DNA Complementar/análise , DNA Complementar/genética , Éxons/genética , Feminino , Marcadores Genéticos , Homozigoto , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Curr Biol ; 9(17): 946-54, 1999 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-10508583

RESUMO

BACKGROUND: Signals from anterior endodermal cells that express the homeobox gene Hex initiate development of the most rostral tissues of the mouse embryo. The dorsal/anterior endoderm of the Xenopus gastrula, which expresses Hex and the putative head-inducing gene cerberus, is proposed to be equivalent to the mouse anterior endoderm. Here, we report the origin and signalling properties of this population of cells in the early Xenopus embryo. RESULTS: Xenopus anterior endoderm was found to derive in part from cells at the centre of the blastocoel floor that express XHex, the Xenopus cognate of Hex. Like their counterparts in the mouse embryo, these Hex-expressing blastomeres moved to the dorsal side of the Xenopus embryo as gastrulation commenced, and populated deep endodermal adjacent to Spemann's organiser. Experiments involving the induction of secondary axes confirmed that XHex expression was associated with anterior development. Ventral misexpression of XHex induced ectopic cerberus expression and conferred anterior signalling properties to the endoderm. Unlike the effect of misexpressing cerberus, these signals could not neuralise overlying ectoderm. CONCLUSIONS: XHex expression reveals the unexpected origin of an anterior signalling centre in Xenopus, which arises in part from the centre of the blastula and localises to the deep endoderm adjacent to Spemann's organiser. Signals originating from these endodermal cells impart an anterior identity to the overlying ectoderm, but are insufficient for neural induction. The anterior movement of Hex-expressing cells in both Xenopus and mouse embryos suggests that this process is a conserved feature of vertebrate development.


Assuntos
Blastocisto/fisiologia , Genes Homeobox , Proteínas de Homeodomínio/fisiologia , Xenopus laevis/embriologia , Animais , Blastocisto/citologia , Blastômeros/citologia , Indução Embrionária/fisiologia , Endoderma/citologia , Gástrula/fisiologia , Gástrula/ultraestrutura , Cabeça/embriologia , Proteínas de Homeodomínio/genética , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Microinjeções , Morfogênese/genética , Especificidade de Órgãos , Proteínas/genética , Proteínas/fisiologia , RNA Mensageiro/administração & dosagem , RNA Mensageiro/genética , Especificidade da Espécie , Fatores de Transcrição , Proteínas de Xenopus , Xenopus laevis/genética
11.
Acta Paediatr Suppl ; 88(433): 49-54, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10626545

RESUMO

The homeobox gene Hesx1, which encodes a pituitary transcription factor, is first expressed at gastrulation in the mouse embryo. Hesx1 expression begins in prospective forebrain tissue but later becomes restricted to Rathke's pouch, the primordium of the anterior pituitary gland. Transgenic mice lacking Hesx1 exhibit a phenotype comprising variable anterior CNS defects, such as a reduced prosencephalon, abnormalities in the corpus callosum and septum pellucidum, anophthalmia or microphthalmia, defective olfactory development and bifurcations in Rathke's pouch with pituitary dysplasia. A comparable and highly variable phenotype in humans is septo-optic dysplasia. We have cloned and sequenced the human homologue HESX1 and screened for mutations in affected individuals using single-stranded conformational polymorphism analysis. Two siblings with septo-optic dysplasia were homozygous for a missense mutation within the HESX1 homeobox. This mutation resulted in the substitution of a highly conserved arginine residue (Arg53) by cysteine and led to a loss of in vitro DNA binding. Hence, a vital role for Hesx1/HESX1 in forebrain and pituitary development in mice and humans is suggested.


Assuntos
Genes Homeobox , Sequências Hélice-Alça-Hélice/genética , Proteínas de Homeodomínio/genética , Septo Pelúcido/anormalidades , Animais , Arginina/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Cisteína/genética , Genótipo , Humanos , Mutação de Sentido Incorreto , Fenótipo , Adeno-Hipófise/fisiologia , Prosencéfalo/fisiologia , Proteínas Repressoras , Fatores de Transcrição HES-1 , Transcrição Gênica
12.
Nat Genet ; 19(2): 125-33, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9620767

RESUMO

During early mouse development the homeobox gene Hesx1 is expressed in prospective forebrain tissue, but later becomes restricted to Rathke's pouch, the primordium of the anterior pituitary gland. Mice lacking Hesx1 exhibit variable anterior CNS defects and pituitary dysplasia. Mutants have a reduced prosencephalon, anopthalmia or micropthalmia, defective olfactory development and bifurcations in Rathke's pouch. Neonates exhibit abnormalities in the corpus callosum, the anterior and hippocampal commissures, and the septum pellucidum. A comparable and equally variable phenotype in humans is septo-optic dysplasia (SOD). We have cloned human HESX1 and screened for mutations in affected individuals. Two siblings with SOD were homozygous for an Arg53Cys missense mutation within the HESX1 homeodomain which destroyed its ability to bind target DNA. These data suggest an important role for Hesx1/HESX1 in forebrain, midline and pituitary development in mouse and human.


Assuntos
Anormalidades Múltiplas/genética , Sequências Hélice-Alça-Hélice/genética , Proteínas de Homeodomínio/genética , Mutação , Hipófise/anormalidades , Septo Pelúcido/anormalidades , Anormalidades Múltiplas/patologia , Alelos , Sequência de Aminoácidos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , DNA/metabolismo , Desenvolvimento Embrionário e Fetal/genética , Feminino , Genótipo , Proteínas de Homeodomínio/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Fases de Leitura Aberta , Nervo Óptico/embriologia , Nervo Óptico/patologia , Linhagem , Hipófise/embriologia , Proteínas Repressoras , Septo Pelúcido/embriologia , Fatores de Transcrição HES-1
13.
Development ; 125(1): 85-94, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9389666

RESUMO

The divergent homeobox gene Hex exhibits three notable expression patterns during early mouse development. Initially Hex is expressed in the primitive endoderm of the implanting blastocyst but by 5.5 dpc its transcripts are present only in a small patch of visceral endoderm at the distal tip of the egg cylinder. Lineage analysis shows that these cells move unilaterally to assume an anterior position while continuing to express Hex. The primitive streak forms on the opposite side of the egg cylinder from this anterior Hex expression domain approximately 24 hours after the initial anterior movement of the distal visceral endoderm. Thus, Hex expression marks the earliest unequivocal molecular anteroposterior asymmetry in the mouse embryo and indicates that the anteroposterior axis of the embryo develops from conversion of a proximodistal asymmetry established in the primitive endoderm lineage. Subsequently, Hex is expressed in the earliest definitive endoderm to emerge from the streak and its expression within the gut strongly suggests that the ventral foregut is derived from the most anterior definitive endoderm and that the liver is probably the most anterior gut derivative. Hex is also an early marker of the thyroid primordium. Within the mesoderm, Hex is transiently expressed in the nascent blood islands of the visceral yolk sac and later in embryonic angioblasts and endocardium. Comparison with flk-1 (T. P. Yamaguchi et al., Development 118, 489-498, 1993) expression indicates that Hex is also an early marker of endothelial precursors but its expression in this progenitor population is much more transient than that of flk-1, being downregulated once endothelial cell differentiation commences.


Assuntos
Padronização Corporal , Embrião de Mamíferos/metabolismo , Endotélio Vascular/citologia , Regulação da Expressão Gênica no Desenvolvimento , Genes Homeobox/genética , Proteínas de Homeodomínio/genética , Animais , Carbocianinas/metabolismo , Diferenciação Celular , Sistema Digestório/embriologia , Desenvolvimento Embrionário e Fetal , Endoderma/fisiologia , Endotélio Vascular/embriologia , Gástrula/fisiologia , Histocitoquímica , Hibridização In Situ , Camundongos , Neovascularização Fisiológica , RNA Mensageiro/análise , Receptores Proteína Tirosina Quinases/genética , Receptores de Fatores de Crescimento/genética , Receptores de Fatores de Crescimento do Endotélio Vascular , Células-Tronco/citologia , Fatores de Transcrição
14.
J Biol Chem ; 270(8): 3869-75, 1995 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-7876132

RESUMO

Extensive analyses of homeobox gene expression and function during murine embryogenesis have demonstrated that homeobox gene products are key components in the establishment of pattern formation and regional identity during development. In this paper we report the molecular characterization and expression of a novel murine homeobox sequence, Hesx1, isolated from pluripotent embryonic stem cells. Hesx1 is expressed as two transcripts of 1.0 and 1.2 kilobases which encode an identical 185 amino acid open reading frame. The transcripts differ in the 3'-untranslated region due to the differential utilization of a weak splice donor site located immediately downstream of the translation termination codon. The Hesx1 homeodomain shared 80% identity with the Xenopus homeoprotein XANF-1 and was less than 50% related to other homeodomain sequences. Hesx1 and XANF-1 therefore constitute the founder members of a new homeodomain class. Hesx1 expression was down-regulated during embryonic stem cell differentiation and was detected in tissue-specific RNA samples derived from the embryonic liver, and at lower levels in viscera, amnion, and yolk sac. Expression in adult mice was not detected. These sites of expression are consistent with a role for Hesx1 in the regulation of developmental decisions in the early mouse embryo and during fetal hematopoiesis.


Assuntos
Genes Homeobox , Proteínas de Homeodomínio/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Diferenciação Celular/genética , Células Cultivadas , DNA Complementar , Éxons , Regulação da Expressão Gênica no Desenvolvimento , Íntrons , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos CBA , Dados de Sequência Molecular , Proteínas Repressoras , Homologia de Sequência de Aminoácidos , Fatores de Transcrição HES-1 , Xenopus
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...