RESUMEN
Radial glial progenitors (RGPs) are elongated epithelial cells that give rise to neurons, glia, and adult stem cells during brain development. RGP nuclei migrate basally during G1, apically using cytoplasmic dynein during G2, and undergo mitosis at the ventricular surface. By live imaging of in utero electroporated rat brain, we find that two distinct G2-specific mechanisms for dynein nuclear pore recruitment are essential for apical nuclear migration. The "RanBP2-BicD2" and "Nup133-CENP-F" pathways act sequentially, with Nup133 or CENP-F RNAi arresting nuclei close to the ventricular surface in a premitotic state. Forced targeting of dynein to the nuclear envelope rescues nuclear migration and cell-cycle progression, demonstrating that apical nuclear migration is not simply correlated with cell-cycle progression from G2 to mitosis, but rather, is a required event. These results reveal that cell-cycle control of apical nuclear migration occurs by motor protein recruitment and identify a role for nucleus- and centrosome-associated forces in mitotic entry. PAPERCLIP:
Asunto(s)
Encéfalo/embriología , Núcleo Celular/metabolismo , Dineínas/metabolismo , Mitosis , Células-Madre Neurales/citología , Poro Nuclear/metabolismo , Animales , Encéfalo/citología , Proteínas Portadoras/metabolismo , Centrosoma/metabolismo , Embrión de Mamíferos/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Asociadas a Microtúbulos , Células-Madre Neurales/metabolismo , Neurogénesis , RatasRESUMEN
During development of the mammalian brain, neural stem cells divide and give rise to adult stem cells, glia and neurons, which migrate to their final locations. Nuclear migration is an important feature of neural stem cell (radial glia progenitor) proliferation and subsequent postmitotic neuronal migration. Defects in nuclear migration contribute to severe neurodevelopmental disorders such as microcephaly and lissencephaly. In this review, we address the cellular and molecular mechanisms responsible for nuclear migration during the radial glia cell cycle and postmitotic neuronal migration, with a particular focus on the role of molecular motors and cytoskeleton dynamics in regulating nuclear behavior.