Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
1.
Cell ; 186(15): 3143-3145, 2023 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-37478818

RESUMEN

Assisted reproduction is on the rise globally. Cell morphology is commonly used for embryo selection, but the cell biology of early preimplantation development remains poorly understood. In this issue of Cell, Domingo-Muelas et al. reveal novel features of human embryos with critical implications for preimplantation genetic testing.


Asunto(s)
Colorantes , Desarrollo Embrionario , Humanos , Blastocisto , Embrión de Mamíferos , Pruebas Genéticas
2.
Biol Cell ; 111(8): 199-212, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30905068

RESUMEN

Motile cilia of epithelial multiciliated cells transport vital fluids along organ lumens to promote essential respiratory, reproductive and brain functions. Progenitors of multiciliated cells undergo massive and coordinated organelle remodelling during their differentiation for subsequent motile ciliogenesis. Defects in multiciliated cell differentiation lead to severe cilia-related diseases by perturbing cilia-based flows. Recent work designated the machinery of mitosis as the orchestrator of the orderly progression of differentiation associated with multiple motile cilia formation. By examining the events leading to motile ciliogenesis with a methodological prism of mitosis, we contextualise and discuss the recent findings to broaden the spectrum of questions related to the differentiation of mammalian multiciliated cells.


Asunto(s)
Centriolos/metabolismo , Cilios/fisiología , Células Epiteliales , Mitosis/fisiología , Orgánulos/metabolismo , Animales , Proteína Quinasa CDC2/metabolismo , Línea Celular , Transformación Celular Neoplásica , Células Epiteliales/citología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Humanos , Ratones , Levaduras/metabolismo
3.
Nature ; 516(7529): 104-7, 2014 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-25307055

RESUMEN

The semi-conservative centrosome duplication in cycling cells gives rise to a centrosome composed of a mother and a newly formed daughter centriole. Both centrioles are regarded as equivalent in their ability to form new centrioles and their symmetric duplication is crucial for cell division homeostasis. Multiciliated cells do not use the archetypal duplication program and instead form more than a hundred centrioles that are required for the growth of motile cilia and the efficient propelling of physiological fluids. The majority of these new centrioles are thought to appear de novo, that is, independently from the centrosome, around electron-dense structures called deuterosomes. Their origin remains unknown. Using live imaging combined with correlative super-resolution light and electron microscopy, we show that all new centrioles derive from the pre-existing progenitor cell centrosome through multiple rounds of procentriole seeding. Moreover, we establish that only the daughter centrosomal centriole contributes to deuterosome formation, and thus to over ninety per cent of the final centriole population. This unexpected centriolar asymmetry grants new perspectives when studying cilia-related diseases and pathological centriole amplification observed in cycling cells and associated with microcephaly and cancer.


Asunto(s)
Centriolos/fisiología , Centrosoma/fisiología , Cilios/fisiología , Animales , Células Cultivadas , Centriolos/ultraestructura , Centrosoma/ultraestructura , Cilios/ultraestructura , Ratones , Microscopía Electrónica de Transmisión
4.
J Vis Exp ; (203)2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38284534

RESUMEN

A major challenge in understanding the causes of female infertility is to elucidate mechanisms governing the development of female germ cells, named oocytes. Their development is marked by cell growth and subsequent divisions, two critical phases that prepare the oocyte for fusion with sperm to initiate embryogenesis. During growth, oocytes reorganize their cytoplasm to position the nucleus at the cell center, an event predictive of successful oocyte development in mice and humans and, thus, their embryogenic potential. In mouse oocytes, this cytoplasmic reorganization was shown to be driven by the cytoskeleton, the activity of which generates mechanical forces that agitate, reposition, and penetrate the nucleus. Consequently, this cytoplasmic-to-nucleoplasmic force transmission tunes the dynamics of nuclear RNA-processing organelles known as biomolecular condensates. This protocol provides an experimental framework to document, with high temporal resolution, the impact of the cytoskeleton on the nucleus across spatial scales in mouse oocytes. It details the imaging and image analysis steps and tools necessary to evaluate i) cytoskeletal activity in the oocyte cytoplasm, ii) cytoskeleton-based agitation of the oocyte nucleus, and iii) its effects on biomolecular condensate dynamics in the oocyte nucleoplasm. Beyond oocyte biology, the methods elaborated here can be adapted for use in somatic cells to similarly address cytoskeleton-based tuning of nuclear dynamics across scales.


Asunto(s)
Citoesqueleto , Semen , Humanos , Masculino , Femenino , Ratones , Animales , Oocitos , Citoplasma , Núcleo Celular
5.
Nat Commun ; 13(1): 5070, 2022 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-36038550

RESUMEN

Cells remodel their cytoplasm with force-generating cytoskeletal motors. Their activity generates random forces that stir the cytoplasm, agitating and displacing membrane-bound organelles like the nucleus in somatic and germ cells. These forces are transmitted inside the nucleus, yet their consequences on liquid-like biomolecular condensates residing in the nucleus remain unexplored. Here, we probe experimentally and computationally diverse nuclear condensates, that include nuclear speckles, Cajal bodies, and nucleoli, during cytoplasmic remodeling of female germ cells named oocytes. We discover that growing mammalian oocytes deploy cytoplasmic forces to timely impose multiscale reorganization of nuclear condensates for the success of meiotic divisions. These cytoplasmic forces accelerate nuclear condensate collision-coalescence and molecular kinetics within condensates. Disrupting the forces decelerates nuclear condensate reorganization on both scales, which correlates with compromised condensate-associated mRNA processing and hindered oocyte divisions that drive female fertility. We establish that cytoplasmic forces can reorganize nuclear condensates in an evolutionary conserved fashion in insects. Our work implies that cells evolved a mechanism, based on cytoplasmic force tuning, to functionally regulate a broad range of nuclear condensates across scales. This finding opens new perspectives when studying condensate-associated pathologies like cancer, neurodegeneration and viral infections.


Asunto(s)
Nucléolo Celular , Núcleo Celular , Animales , Cuerpos Enrollados , Citoplasma , Femenino , Mamíferos , Oocitos
7.
Sci Rep ; 9(1): 13060, 2019 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-31506528

RESUMEN

Reproductive and respiratory organs, along with brain ventricles, are lined by multiciliated epithelial cells (MCC) that generate cilia-powered fluid flows. MCC hijack the centrosome duplication pathway to form hundreds of centrioles and nucleate motile cilia. In these cells, the large majority of procentrioles are formed associated with partially characterized organelles called deuterosomes. We recently challenged the paradigm that deuterosomes and procentrioles are formed de novo by providing data, in brain MCC, suggesting that they are nucleated from the pre-existing centrosomal younger centriole. However, the origin of deuterosomes and procentrioles is still under debate. Here, we further question centrosome importance for deuterosome and centriole amplification. First, we provide additional data confirming that centriole amplification occurs sequentially from the centrosomal region, and that the first procentriole-loaded deuterosomes are associated with the daughter centriole or in the centrosomal centriole vicinity. Then, to further test the requirement of the centrosome in deuterosome and centriole formation, we depleted centrosomal centrioles using a Plk4 inhibitor. We reveal unexpected limited consequences in deuterosome/centriole number in absence of centrosomal centrioles. Notably, in absence of the daughter centriole only, deuterosomes are not seen associated with the mother centriole. In absence of both centrosomal centrioles, procentrioles are still amplified sequentially and with no apparent structural defects. They seem to arise from a focal region, characterized by microtubule convergence and pericentriolar material (PCM) assembly. The relevance of deuterosome association with the daughter centriole as well as the role of the PCM in the focal and sequential genesis of centrioles in absence of centrosomal centrioles are discussed.


Asunto(s)
Encéfalo/fisiología , Centriolos/metabolismo , Centrosoma/metabolismo , Cilios/metabolismo , Células Epiteliales/metabolismo , Biomarcadores , Ciclo Celular , Técnica del Anticuerpo Fluorescente , Humanos , Imagen Molecular , Orgánulos/metabolismo
8.
Dev Cell ; 51(2): 145-157.e10, 2019 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-31607652

RESUMEN

Nucleus position in cells can act as a developmental cue. Mammalian oocytes position their nucleus centrally using an F-actin-mediated pressure gradient. The biological significance of nucleus centering in mammalian oocytes being unknown, we sought to assess the F-actin pressure gradient effect on the nucleus. We addressed this using a dedicated computational 3D imaging approach, biophysical analyses, and a nucleus repositioning assay in mouse oocytes mutant for cytoplasmic F-actin. We found that the cytoplasmic activity, in charge of nucleus centering, shaped the nucleus while promoting nuclear envelope fluctuations and chromatin motion. Off-centered nuclei in F-actin mutant oocytes were misshaped with immobile chromatin and modulated gene expression. Restoration of F-actin in mutant oocytes rescued nucleus architecture fully and gene expression partially. Thus, the F-actin-mediated pressure gradient also modulates nucleus dynamics in oocytes. Moreover, this study supports a mechano-transduction model whereby cytoplasmic microfilaments could modulate oocyte transcriptome, essential for subsequent embryo development.


Asunto(s)
Citoesqueleto de Actina/metabolismo , Citoplasma/metabolismo , Membrana Nuclear/metabolismo , Oocitos/metabolismo , Actinas/metabolismo , Animales , Núcleo Celular/metabolismo , Cromatina/metabolismo , Femenino , Masculino , Meiosis/fisiología , Ratones Transgénicos
9.
Curr Biol ; 28(17): R948-R951, 2018 09 10.
Artículo en Inglés | MEDLINE | ID: mdl-30205069

RESUMEN

A single bipolar spindle was thought to form around both parental genomes in zygotes initiating the first division. A recent study challenges this predominant view by showing that two independent spindles assemble to prevent parental genome mixing in mouse zygotes.


Asunto(s)
Embrión de Mamíferos , Cigoto , Animales , Genoma , Humanos , Ratones , Mitosis , Padres
10.
Science ; 358(6364): 803-806, 2017 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-28982797

RESUMEN

Cell division and differentiation depend on massive and rapid organelle remodeling. The mitotic oscillator, centered on the cyclin-dependent kinase 1-anaphase-promoting complex/cyclosome (CDK1-APC/C) axis, spatiotemporally coordinates this reorganization in dividing cells. Here we discovered that nondividing cells could also implement this mitotic clocklike regulatory circuit to orchestrate subcellular reorganization associated with differentiation. We probed centriole amplification in differentiating mouse-brain multiciliated cells. These postmitotic progenitors fine-tuned mitotic oscillator activity to drive the orderly progression of centriole production, maturation, and motile ciliation while avoiding the mitosis commitment threshold. Insufficient CDK1 activity hindered differentiation, whereas excessive activity accelerated differentiation yet drove postmitotic progenitors into mitosis. Thus, postmitotic cells can redeploy and calibrate the mitotic oscillator to uncouple cytoplasmic from nuclear dynamics for organelle remodeling associated with differentiation.


Asunto(s)
Ciclosoma-Complejo Promotor de la Anafase/metabolismo , Proteína Quinasa CDC2/metabolismo , Cilios/fisiología , Mitosis , Animales , Encéfalo/citología , Diferenciación Celular , Centriolos/metabolismo , Ratones , Orgánulos/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA