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1.
Development ; 149(5)2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35132995

RESUMEN

Distinct neural stem cells (NSCs) reside in different regions of the subventricular zone (SVZ) and generate multiple olfactory bulb (OB) interneuron subtypes in the adult brain. However, the molecular mechanisms underlying such NSC heterogeneity remain largely unknown. Here, we show that the basic helix-loop-helix transcription factor Olig2 defines a subset of NSCs in the early postnatal and adult SVZ. Olig2-expressing NSCs exist broadly but are most enriched in the ventral SVZ along the dorsoventral axis complementary to dorsally enriched Gsx2-expressing NSCs. Comparisons of Olig2-expressing NSCs from early embryonic to adult stages using single cell transcriptomics reveal stepwise developmental changes in their cell cycle and metabolic properties. Genetic studies further show that cross-repression contributes to the mutually exclusive expression of Olig2 and Gsx2 in NSCs/progenitors during embryogenesis, but that their expression is regulated independently from each other in adult NSCs. Finally, lineage-tracing and conditional inactivation studies demonstrate that Olig2 plays an important role in the specification of OB interneuron subtypes. Altogether, our study demonstrates that Olig2 defines a unique subset of adult NSCs enriched in the ventral aspect of the adult SVZ.


Asunto(s)
Interneuronas/metabolismo , Ventrículos Laterales/crecimiento & desarrollo , Ventrículos Laterales/metabolismo , Células-Madre Neurales/metabolismo , Bulbo Olfatorio/crecimiento & desarrollo , Bulbo Olfatorio/metabolismo , Factor de Transcripción 2 de los Oligodendrocitos/metabolismo , Animales , Ciclo Celular/genética , Linaje de la Célula/genética , Células Cultivadas , Femenino , Técnicas de Inactivación de Genes , Ventrículos Laterales/embriología , Masculino , Ratones , Ratones Noqueados , Neurogénesis/genética , Bulbo Olfatorio/embriología , Factor de Transcripción 2 de los Oligodendrocitos/genética , Transducción de Señal/genética , Transcriptoma/genética
2.
Am J Physiol Lung Cell Mol Physiol ; 313(5): L733-L740, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28798251

RESUMEN

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users.


Asunto(s)
Bases de Datos Genéticas , Redes Reguladoras de Genes/genética , Pulmón/crecimiento & desarrollo , Organogénesis/genética , Proteómica , Animales , Humanos , Proteómica/métodos , Regeneración/genética
3.
Development ; 134(10): 1873-85, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17428831

RESUMEN

Drosophila Pygopus was originally identified as a core component of the canonical Wnt signaling pathway and a transcriptional coactivator. Here we have investigated the microophthalmia that arises in mice with a germline null mutation of pygopus 2. We show that this phenotype is a consequence of defective lens development at inductive stages. Using a series of regionally limited Cre recombinase transgenes for conditional deletion of Pygo2(flox), we show that Pygo2 activity in pre-placodal presumptive lens ectoderm, placodal ectoderm and ocular mesenchyme all contribute to lens development. In each case, Pygo2 is required for normal expression levels of the crucial transcription factor Pax6. Finally, we provide multiple lines of evidence that although Pygo2 can function in the Wnt pathway, its activity in lens development is Wnt pathway-independent.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Péptidos y Proteínas de Señalización Intracelular/fisiología , Cristalino/embriología , Proteínas Wnt/metabolismo , Alelos , Animales , Proteínas del Ojo/metabolismo , Proteínas de Homeodominio/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Mesodermo/metabolismo , Ratones , Ratones Mutantes , Ratones Transgénicos , Modelos Genéticos , Cresta Neural/citología , Factor de Transcripción PAX6 , Factores de Transcripción Paired Box/metabolismo , Fenotipo , Proteínas Represoras/metabolismo , Transducción de Señal
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