Biology subjects

Yue, Z.

Publications and source records attributed to Yue, Z..

4 recordsLinked to original sources

bioRxiv2018

Live-cell imaging of marked chromosome regions reveals dynamics of mitotic chromosome resolution and compaction

When human cells enter mitosis, chromosomes undergo substantial changes in their organisation to resolve sister chromatids and compact chromosomes. Despite the fundamental importance of this phenomenon to genome stability, we still do not fully comprehend the timing and coordination of these events. To address these questions, we need to evaluate the progression of both sister chromatid resolution and chromosome compaction in one assay. We achieved this by analysing changes in configuration of marked chromosome regions over time, with high spatial and temporal resolution. This assay showed that sister chromatid resolution is an iterative process that begins in late G2 phase and completes in prophase. Cohesins and WAPL antagonistically regulate sister chromatid resolution in late G2 and prophase whilst local enrichment of cohesin on chromosomes prevents precocious sister chromatid resolution. Moreover, our assay allowed quantitative evaluation of the timing and efficiency of condensin II and I activities in promoting sister chromatid resolution and chromosome compaction, respectively. Thus, our real-time assay sheds new light on the dynamics of mitotic chromosome resolution and compaction.

cell biology↗

bioRxiv2018

A new approach to design artificial 3D micro-niches with combined chemical, topographical and rheological cues

The in vitro methods to recapitulate environmental cues around cells are usually optimized to test a specific property of the environment (biochemical nature or the stiffness of the extra cellular matrix (ECM), or nanotopography) for its capability to induce defined cell behaviors (lineage commitment, migration). Approaches that combine different environmental cues in 3D to assess the biological response of cells to the spatial organization of different biophysical and biochemical cues are growingly being developed. We demonstrate how the lamination of through-hole polymeric bio-functionalized membranes can be implemented to create complex bona fide micro-niches with differential 3D environmental properties using photoactive materials. Our approach enables to create micro-niches ranging in size from single cells to cell aggregates. They are bio-functionalized in 3D simultaneously with topographical featured, protein patterns and structured ECM surrogate with 1 micrometer resolution. We demonstrate how these niches extend in 3D the ability to pattern cells. We exemplify how they can be used to standardize cells shapes in 3D and to trigger the apico-basal polarization of single epithelial cells.

bioengineering↗

bioRxiv2017

Haploinsufficiency of Parkinsonism Gene SYNJ1 Contributes to Dopamine neuron Vulnerability in Aged Mice

Parkinsons disease (PD) is an age-dependent neurodegenerative disorder characterized by the loss of substantia nigra dopaminergic (DAergic) neurons in ventral midbrain (MB). Identification of interactions between aging and the known risk variants is crucial to understanding the etiology of PD. Recessive mutations in SYNJ1 have recently been linked to familial early-onset atypical Parkinsonism. We now show an age-dependent decline of SYNJ1 expression in the striatum as well as in striatal DAergic terminals of aged mice. Heterozygous deletion of SYNJ1 in mice causes selective elevation of PIP2 in the MB, and manipulation of PIP2 levels also impairs synaptic vesicle recycling preferentially in MB neurons. SYNJ1+/- mice display progressive PD-like behavioral alterations and DAergic terminal degeneration. Furthermore, we found down-regulation of human SYNJ1 transcripts in a subset of sporadic PD brains, corroborating the role of an age-dependent decrease in SYNJ1 in predisposing DAergic neuron vulnerability and PD pathogenesis.

neuroscience↗

bioRxiv2017

A circadian clock in the blood-brain barrier regulates xenobiotic efflux from the brain

HighlightsO_LIThe Drosophila BBB displays a circadian rhythm of permeability\nC_LIO_LICyclic efflux driven by a clock in the BBB underlies the permeability rhythm\nC_LIO_LICircadian control is non-cell-autonomous via gap junction regulation of [Mg2+]i\nC_LIO_LIAn anti-seizure drug is more effective when administered at night\nC_LI\n\nSummaryEndogenous circadian rhythms are thought to modulate responses to external factors, but mechanisms that confer time-of-day differences in organismal responses to environmental insults / therapeutic treatments are poorly understood. Using a xenobiotic, we find that permeability of the Drosophila \"blood\"-brain barrier (BBB) is higher at night. The permeability rhythm is driven by circadian regulation of efflux and depends upon a molecular clock in the perineurial glia of the BBB, although efflux transporters are restricted to subperineurial glia (SPG). We show that transmission of circadian signals across the layers requires gap junctions, which are expressed cyclically. Specifically, during nighttime gap junctions reduce intracellular magnesium ([Mg2+]i), a positive regulator of efflux, in SPG. Consistent with lower nighttime efflux, nighttime administration of the anti-epileptic phenytoin is more effective at treating a Drosophila seizure model. These findings identify a novel mechanism of circadian regulation and have therapeutic implications for drugs targeted to the central nervous system.

neuroscience↗