0000000000179154

AUTHOR

Alexandra Bizy

Evolutionary conserved role of eukaryotic translation factor eIF5A in the regulation of actin-nucleating formins

AbstractElongation factor eIF5A is required for the translation of consecutive prolines, and was shown in yeast to translate polyproline-containing Bni1, an actin-nucleating formin required for polarized growth during mating. Here we show that Drosophila eIF5A can functionally replace yeast eIF5A and is required for actin-rich cable assembly during embryonic dorsal closure (DC). Furthermore, Diaphanous, the formin involved in actin dynamics during DC, is regulated by and mediates eIF5A effects. Finally, eIF5A controls cell migration and regulates Diaphanous levels also in mammalian cells. Our results uncover an evolutionary conserved role of eIF5A regulating cytoskeleton-dependent processes…

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Epigenetic regulation of stemness maintenance in the neurogenic niches

In the adult mouse brain, the subventricular zone lining the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus are two zones that contain neural stem cells (NSCs) with the capacity to give rise to neurons and glia during the entire life of the animal. Spatial and temporal regulation of gene expression in the NSCs population is established and maintained by the coordinated interaction between transcription factors and epigenetic regulators which control stem cell fate. Epigenetic mechanisms are heritable alterations in genome function that do not involve changes in DNA sequence itself but that modulate gene expression, acting as mediators between the environ…

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Isolation, Long-Term Expansion, and Differentiation of Murine Neural Stem Cells

Stem cells are capable of extensive self-renewal while preserving the ability to generate cell progeny that can differentiate into different cell types. Here, we describe some methods for the isolation of neural stem cells (NSCs) from the adult murine subependymal zone (SEZ), their extensive culturing and the assessment of their full developmental potential, particularly with respect to their differentiation capacity. The procedure includes chemically defined conditions such as absence of serum and addition of specific growth factors, in which differentiated cells die and are rapidly eliminated from the culture. In contrast, undifferentiated precursors become hypertrophic and proliferate, f…

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p73 is required for ependymal cell maturation and neurogenic SVZ cytoarchitecture

The adult subventricular zone (SVZ) is a highly organized microenvironment established during the first postnatal days when radial glia cells begin to transform into type B-cells and ependymal cells, all of which will form regenerative units, pinwheels, along the lateral wall of the lateral ventricle. Here, we identify p73, a p53 homologue, as a critical factor controlling both cell-type specification and structural organization of the developing mouse SVZ. We describe that p73 deficiency halts the transition of the radial glia into ependymal cells, leading to the emergence of immature cells with abnormal identities in the ventricle and resulting in loss of the ventricular integrity. p73-de…

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