Biology subjects

Glise, B.

Publications and source records attributed to Glise, B..

3 recordsLinked to original sources

bioRxiv2023

Modelling variability and heterogeneity of EMT scenarios highlights nuclear positioning and protrusions as main drivers of extrusion

Epithelial-Mesenchymal Transition (EMT) is a key process in physiological and pathological settings (i.e. development, fibrosis, cancer). EMT is often presented as a linear sequence of events including (i) disassembly of cell-cell junctions, (ii) loss of epithelial polarity and (iii) reorganization of the cytoskeleton leading to basal extrusion from the epithelium. Once out, cells can adopt a migratory phenotype with a front-rear polarity and may additionally become invasive. While this stereotyped sequence can occur, many in vivo observations have challenged this notion. It is now accepted that there are multiple EMT scenarios and that cell populations implementing EMT are often heterogeneous. However, the relative importance of each EMT step towards extrusion is unclear. Similarly, the overall impact of variability and heterogeneity on the efficiency and directionality of cell extrusion has not been assessed. Here we used computational modelling of a pseudostratified epithelium to model multiple EMT-like scenarios. We confronted these in silico data to the EMT occurring during neural crest delamination. Overall, our simulated and biological data point to a key role of nuclear positioning and protrusive activity to generate timely basal extrusion of cells and suggest a non-linear model of EMT allowing multiple scenarios to co-exist.

developmental biology↗

bioRxiv2020

Sulf2a controls Shh-dependent neural fate specification in the developing spinal cord

Sulf2a belongs to the Sulf family of extracellular sulfatases which selectively remove 6-O-sulfate groups from heparan sulfates, a critical regulation level for their role in modulating the activity of signalling molecules. Data presented here define Sulf2a as a novel player in the control of Sonic Hedgehog (Shh)-mediated cell type specification during spinal cord development. We show that Sulf2a depletion in zebrafish results in overproduction of V3 interneurons at the expense of motor neurons and also impedes generation of oligodendrocyte precursor cells (OPCs), three cell types that depend on Shh for their generation. We provide evidence that Sulf2a, expressed in a spatially restricted progenitor domain, acts by maintaining the correct patterning and specification of ventral progenitors. More specifically, Sulf2a prevents Olig2 progenitors to activate high-threshold Shh response and, thereby, to adopt a V3 interneuron fate, thus ensuring proper production of motor neurons and OPCs. We propose a model in which Sulf2a reduces Shh signalling levels in responding cells by decreasing their sensitivity to the morphogen factor. More generally, our work, revealing that, in contrast to its paralog Sulf1, Sulf2a regulates neural fate specification in Shh target cells, provides direct evidence of non-redundant functions of Sulfs in the developing spinal cord.

developmental biology↗

bioRxiv2018

Identification of a Sulf2-dependant astrocyte subtype that stands out through the expression of Olig2 in the ventral spinal cord

During spinal cord development, both spatial and temporal mechanisms operate to generate glial cell diversity. Here, we addressed the role of the Heparan Sulfate-editing enzyme Sulf2 in the control of gliogenesis in the mouse developing spinal cord and found an unanticipated function for this enzyme. Sulf2 is expressed in ventral spinal progenitors at initiation of gliogenesis, including in Olig2-expressing cells of the pMN domain known to generate most spinal cord oligodendrocyte precursor cells (OPCs). We found that Sulf2 is dispensable for OPC development but required for proper generation of an as-yet-unidentified astrocyte precursor cell (AP) subtype. These cells, like OPCs, express Olig2 while populating the spinal parenchyma at embryonic stages but also retain Olig2 expression as they differentiate into mature astrocytes. We therefore identify a spinal Olig2-expressing AP subtype that segregates early under the influence of the extracellular enzyme Sulf2.

developmental biology↗