RESUMEN
Proliferation and differentiation are tightly controlled during neural development. In the embryonic neural plate, primary neurogenesis is driven by the proneural pathway. Here we report the characterization of Maturin, a novel, evolutionarily conserved protein that is required for normal primary neurogenesis. Maturin is detected throughout the early nervous system, yet it is most strongly expressed in differentiating neurons of the embryonic fish, frog and mouse nervous systems. Maturin expression can be induced by the proneural transcription factors Neurog2, Neurod1, and Ebf3. Maturin overexpression promotes neurogenesis, while loss-of-function inhibits the differentiation of neuronal progenitors, resulting in neural plate expansion. Maturin knockdown blocks the ability of Neurog2, Neurod1, and Ebf3 to drive ectopic neurogenesis. Maturin and Pak3, are both required for, and can synergize to promote differentiation of the primary neurons in vivo. Together, our results suggest that Maturin functions during primary neurogenesis and is required for the proneural pathway to regulate neural differentiation.
Asunto(s)
Diferenciación Celular , Proteínas del Tejido Nervioso/genética , Neuronas/metabolismo , Proteínas de Xenopus/genética , Proteínas de Pez Cebra/genética , Secuencia de Aminoácidos , Animales , Embrión no Mamífero/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica , Ratones , Datos de Secuencia Molecular , Proteínas del Tejido Nervioso/metabolismo , Neurogénesis/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis , Pez Cebra , Proteínas de Pez Cebra/metabolismoRESUMEN
The iDA Project (iPSCs to Study Diversity in Alzheimer's and Alzheimer's Disease-related Dementias) is generating 200 induced pluripotent stem cell lines from Alzheimer's Disease Neuroimaging Initiative participants. These lines are sex balanced, include common APOE genotypes, span disease stages, and are ancestrally diverse. Cell lines and characterization data will be shared openly.
Asunto(s)
Enfermedad de Alzheimer , Células Madre Pluripotentes Inducidas , Humanos , Enfermedad de Alzheimer/genética , Neuroimagen/métodos , Línea CelularRESUMEN
Cortical development in humans is a long and ongoing process that continuously modifies the neural circuitry into adolescence. This is well represented by the dynamic maturation of the corpus callosum, the largest white matter tract in the brain. Callosal projection neurons whose long-range axons form the main component of the corpus callosum are evolved relatively recently with a substantial, disproportionate increase in numbers in humans. Though the anatomy of the corpus callosum and cellular processes in its development have been intensively studied by experts in a variety of fields over several decades, the whole picture of its development, in particular, the molecular controls over the development of callosal projections, still has many missing pieces. This review highlights the most recent progress on the understanding of corpus callosum formation with a special emphasis on the novel molecular players in the development of axonal projections in the corpus callosum.