Assuntos
Encéfalo , Neuroglia , Neurociências/história , História do Século XX , História do Século XXI , Estados UnidosRESUMO
Some of the most interesting questions in biology today, in my view, derive from the real advances in neuropsychiatry that have come largely from human genetics. Research in autism spectrum disorders (ASDs) has been leading the way, mainly because it has become especially well funded and has recently attracted many outstanding scientists. (I must make it clear that I am an outsider in this field, as I have never worked on any neuropsychiatric disorder).
Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Animais , Criança , Modelos Animais de Doenças , Humanos , Sinapses/metabolismoRESUMO
In this Perspective, I review my scientific career, which began after I trained in medicine in Montreal and in neurology in Boston. I started in immunology in London with Avrion Mitchison, using antibodies against cell-surface antigens to study the development and functions of mouse T and B cells. The finding that antibody binding causes immunoglobulin on B cells to redistribute rapidly on the cell surface and be endocytosed transformed me from an immunologist into a cell biologist. I moved with Mitchison to University College London, where my colleagues and I used the antibody approach to study cells of the rodent nervous system, focusing on the intrinsic and extrinsic molecular mechanisms that control the development and behavior of myelinating glial cells-Schwann cells and oligodendrocytes. I retired from active research in 2002 and now spend much of my time on scientific advisory boards and thinking about autism.
Assuntos
Pesquisadores , Animais , Antígenos de Superfície/imunologia , Transtorno Autístico , Linfócitos B/citologia , Linfócitos B/imunologia , Canadá , Morte Celular , Humanos , Imunoglobulinas/metabolismo , Londres , Oligodendroglia/citologia , Oligodendroglia/imunologia , Células de Schwann/citologia , Células de Schwann/imunologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Linfócitos T/citologia , Linfócitos T/imunologia , Estados UnidosRESUMO
The combination of human genetics, animal models, and induced pluripotent stem cells is likely to revolutionize our understanding of neuropsychiatric disorders, leading to new therapies and insights into how the normal human brain works. This is the territory I would explore if I were starting my research career today.
Assuntos
Encéfalo/fisiologia , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Animais , Criança , Modelos Animais de Doenças , Humanos , Neurobiologia/tendênciasRESUMO
Oligodendrocytes develop from proliferating oligodendrocyte precursor cells (OPCs), which arise in germinal zones, migrate throughout the developing white matter and divide a limited number of times before they terminally differentiate. Thus far, it has been possible to purify OPCs only from the rat optic nerve, but the purified cells cannot be obtained in large enough numbers for conventional biochemical analyses. Moreover, the central nervous system stem cells that give rise to OPCs have not been purified, limiting the ability to study the earliest stages of commitment to the oligodendrocyte lineage. Pluripotent mouse embryonic stem (ES) cells can be propagated indefinitely in culture and induced to differentiate into various cell types. We describe protocols for culture conditions in which neural precursor cells, OPCs, and oligodendrocytes can be efficiently produced from genetically modified ES cells. This strategy should be useful for study of the intracellular and extracellular factors that direct central nervous system stem cells down the oligodendrocyte pathway and influence subsequent oligodendrocyte differentiation. It may also be useful for producing OPCs and oligodendrocytes from human ES cells for cell therapy and drug screening.
Assuntos
Técnicas de Cultura de Células , Oligodendroglia/fisiologia , Células-Tronco/fisiologia , Animais , Diferenciação Celular/fisiologia , Linhagem da Célula , Células Cultivadas , Embrião de Mamíferos/citologia , Humanos , Camundongos , Oligodendroglia/citologia , Ratos , Células-Tronco/citologiaRESUMO
We showed previously that purified rat oligodendrocyte precursor cells (OPCs) can be induced by extracellular signals to convert to multipotent neural stem-like cells (NSLCs), which can then generate both neurons and glial cells. Because the conversion of precursor cells to stem-like cells is of both intellectual and practical interest, it is important to understand its molecular basis. We show here that the conversion of OPCs to NSLCs depends on the reactivation of the sox2 gene, which in turn depends on the recruitment of the tumor suppressor protein Brca1 and the chromatin-remodeling protein Brahma (Brm) to an enhancer in the sox2 promoter. Moreover, we show that the conversion is associated with the modification of Lys 4 and Lys 9 of histone H3 at the same enhancer. Our findings suggest that the conversion of OPCs to NSLCs depends on progressive chromatin remodeling, mediated in part by Brca1 and Brm.
Assuntos
Diferenciação Celular , Cromatina/metabolismo , Histonas/metabolismo , Oligodendroglia/citologia , Células-Tronco/citologia , Animais , Sequência de Bases , Proliferação de Células , Primers do DNA , Imuno-Histoquímica , Imunoprecipitação , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A response to Cooper S: Control and maintenance of mammalian cell size. BMC Cell Biol 2004, 5:35.
