RESUMO
Maintenance of stemness is tightly linked to cell cycle regulation through protein phosphorylation by cyclin-dependent kinases (CDKs). However, how this process is reversed during differentiation is unknown. We report here that exit from stemness and differentiation of pluripotent cells along the neural lineage are controlled by CDC14, a CDK-counteracting phosphatase whose function in mammals remains obscure. Lack of the two CDC14 family members, CDC14A and CDC14B, results in deficient development of the neural system in the mouse and impairs neural differentiation from embryonic stem cells (ESCs). Mechanistically, CDC14 directly dephosphorylates specific proline-directed Ser/Thr residues of undifferentiated embryonic transcription Factor 1 (UTF1) during the exit from stemness, triggering its proteasome-dependent degradation. Multiomic single-cell analysis of transcription and chromatin accessibility in differentiating ESCs suggests that increased UTF1 levels in the absence of CDC14 prevent the proper firing of bivalent promoters required for differentiation. CDC14 phosphatases are dispensable for mitotic exit, suggesting that CDC14 phosphatases have evolved to control stemness rather than cell cycle exit and establish the CDK-CDC14 axis as a critical molecular switch for linking cell cycle regulation and self-renewal.
Assuntos
Proteínas de Ciclo Celular , Proteínas de Saccharomyces cerevisiae , Animais , Camundongos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Tirosina Fosfatases/genética , Proteínas Tirosina Fosfatases/metabolismo , Quinases Ciclina-Dependentes/metabolismo , Ciclo Celular , Fosforilação/fisiologia , Mitose , Proteínas de Saccharomyces cerevisiae/metabolismo , MamíferosRESUMO
Naming faces is a common area of study from a wide range of perspectives in social sciences, including cognitive psychology and several branches of cognitive neuroscience. This paper provides a comprehensive review of the cognitive models that have been proposed to explain the diverse aspects of face naming, taking into account face processing and language production models. In addition, a review of the neuroscientific data from event-related potential studies (when) and functional neuroimaging studies (where) is presented. Thus, an integrated view of the cognitive models and the data relating the different processes involved in naming faces to the brain activity is provided.
Assuntos
Córtex Cerebral/fisiologia , Face , Rememoração Mental/fisiologia , Modelos Neurológicos , Modelos Psicológicos , Nomes , Reconhecimento Psicológico/fisiologia , Mapeamento Encefálico , Potenciais Evocados/fisiologia , Humanos , Comunicação Interdisciplinar , Idioma , Imageamento por Ressonância Magnética , Reconhecimento Visual de Modelos/fisiologia , Prosopagnosia/fisiopatologia , Prosopagnosia/psicologia , Percepção Visual/fisiologiaRESUMO
Naming faces is a common area of study from a wide range of perspectives in social sciences, including cognitive psychology and several branches of cognitive neuroscience. This paper provides a comprehensive review of the cognitive models that have been proposed to explain the diverse aspects of face naming, taking into account face processing and language production models. In addition, a review of the neuroscientific data from event-related potential studies (when) and functional neuroimaging studies (where) is presented. Thus, an integrated view of the cognitive models and the data relating the different processes involved in naming faces to the brain activity is provided (AU)
La denominación de caras es un área de interés para diversas perspectivas en ciencias sociales, incluyendo la psicología cognitiva y diversas ramas de neurociencia cognitiva. Este artículo proporciona una revisión de los modelos cognitivos que han sido propuestos para explicar los diversos aspectos de la denominación de caras. Además, se presenta una revisión de los datos neurocientíficos de potenciales evocados (cuándo) y de estudios de neuroimagen funcional (dónde). Así, se presenta una visión integrada de los modelos cognitivos y los datos relacionando los distintos procesos implicados en la denominación de caras y la actividad cerebral (AU)
