14 research outputs found
Cell-to-cell heterogeneity in Sox2 and Bra expression guides progenitor motility and destiny.
Although cell-to-cell heterogeneity in gene and protein expression within cell populations has been widely documented, we know little about its biological functions. By studying progenitors of the posterior region of bird embryos, we found that expression levels of transcription factors Sox2 and Bra, respectively involved in neural tube (NT) and mesoderm specification, display a high degree of cell-to-cell heterogeneity. By combining forced expression and downregulation approaches with time-lapse imaging, we demonstrate that Sox2-to-Bra ratio guides progenitor's motility and their ability to stay in or exit the progenitor zone to integrate neural or mesodermal tissues. Indeed, high Bra levels confer high motility that pushes cells to join the paraxial mesoderm, while high levels of Sox2 tend to inhibit cell movement forcing cells to integrate the NT. Mathematical modeling captures the importance of cell motility regulation in this process and further suggests that randomness in Sox2/Bra cell-to-cell distribution favors cell rearrangements and tissue shape conservation
Sulfatase 2 promotes generation of a spinal cord astrocyte subtype that stands out through the expression of Olig2
International audienc
Study of the Cytolethal Distending Toxin-Induced Cell Cycle Arrest in HeLa Cells: Involvement of the CDC25 Phosphatase
International audienc
Cell-to-cell heterogeneity in Sox2 and Brachyury expression guides progenitor destiny by controlling their movements
Although cell-to-cell heterogeneity in gene and protein expression has been widely documented within a given cell population, little is known about its potential biological functions. We addressed this issue by studying posterior progenitors, an embryonic cell population that is central to vertebrate posterior axis formation. These progenitors are able to maintain themselves within the posterior region of the embryo or to exit this region to participate in the formation of neural tube or paraxial mesoderm tissues. Posterior progenitors are known to co-express transcription factors related to neural and mesodermal lineages, e.g. Sox2 and Brachyury (Bra), respectively. In this study, we find that expression levels of Sox2 and Bra proteins display a high degree of variability among posterior progenitors of the quail embryo, therefore highlighting spatial heterogeneity of this cell population. By over-expression/down-regulation experiments and time-lapse imaging, we show that Sox2 and Bra are both involved in controlling progenitor motility, acting however in an opposite way: while Bra is necessary to progenitor motion, Sox2 tends to inhibit cell movement. Combining mathematical modeling and experimental approaches, we provide evidence that the spatial heterogeneity of posterior progenitors, with regards to their expression levels of Sox2 and Bra and thus to their motile properties, is fundamental to maintain a pool of resident progenitors while others segregate to contribute to tissue formation. As a whole, our work reveals that heterogeneity among a population of progenitor cells is critical to ensure robust multi-tissue morphogenesis
Eph/Ephrin Signaling Controls Progenitor Identities In The Ventral Spinal Cord
Abstract Background In the vertebrate spinal cord, motor neurons (MN) are generated in stereotypical numbers from a pool of dedicated progenitors (pMN) whose number depends on signals that control their specification but also their proliferation and differentiation rates. Although the initial steps of pMN specification have been extensively studied, how pMN numbers are regulated over time is less well characterized. Results Here, we show that ephrinB2 and ephrinB3 are differentially expressed in progenitor domains in the ventral spinal cord with several Eph receptors more broadly expressed. Genetic loss-of-function analyses show that ephrinB2 and ephrinB3 inversely control pMN numbers and that these changes in progenitor numbers correlate with changes in motor neuron numbers. Detailed phenotypic analyses by immunostaining and genetic interaction studies between ephrinB2 and Shh indicate that changes in pMN numbers in ephrin mutants are due to alteration in progenitor identity at late stages of development. Conclusions Altogether our data reveal that Eph:ephrin signaling is required to control progenitor identities in the ventral spinal cord
Comparative modifications in bacterial gill-endosymbiotic populations of the two bivalves Codakia orbiculata and Lucina pensylvanica during bacterial loss and reacquisition
International audienceUntil now, the culture of sulphur-oxidizing bacterial symbionts associated with marine invertebrates remains impossible. Therefore, few studies focused on symbiont's physiology under stress conditions. In this study, we carried out a comparative experiment based on two different species of lucinid bivalves (Codakia orbiculata and Lucina pensylvanica) under comparable stress factors. The bivalves were starved for 6months in sulphide-free filtered seawater. For C.orbiculata only, starved individuals were then put back to the field, in natural sediment. We used in situ hybridization, flow cytometry and X-ray fluorescence to characterize the symbiont population hosted in the gills of both species. In L.pensylvanica, no decrease in symbiont abundance was observed throughout the starvation experiment, whereas elemental sulphur slowly decreased to zero after 3months of starvation. Conversely, in C.orbiculata, symbiont abundance within bacteriocytes decreased rapidly and sulphur from symbionts disappeared during the first weeks of the experiment. The modifications of the cellular characteristics (SSC - relative cell size and FL1 - genomic content) of the symbiotic populations along starvation were not comparable between species. Return to the sediment of starved C.orbiculata individuals led to a rapid (2-4weeks) recovery of symbiotic cellular characteristics, comparable with unstressed symbionts. These results suggest that endosymbiotic population regulation is host-species-dependent in lucinids
FGF signaling controls Shh-dependent oligodendroglial fate specification in the ventral spinal cord
Abstract Background Most oligodendrocytes of the spinal cord originate from ventral progenitor cells of the pMN domain, characterized by expression of the transcription factor Olig2. A minority of oligodendrocytes is also recognized to emerge from dorsal progenitors during fetal development. The prevailing view is that generation of ventral oligodendrocytes depends on Sonic hedgehog (Shh) while dorsal oligodendrocytes develop under the influence of Fibroblast Growth Factors (FGFs). Results Using the well-established model of the chicken embryo, we show that ventral spinal progenitor cells activate FGF signaling at the onset of oligodendrocyte precursor cell (OPC) generation. Inhibition of FGF receptors at that time appears sufficient to prevent generation of ventral OPCs, highlighting that, in addition to Shh, FGF signaling is required also for generation of ventral OPCs. We further reveal an unsuspected interplay between Shh and FGF signaling by showing that FGFs serve dual essential functions in ventral OPC specification. FGFs are responsible for timely induction of a secondary Shh signaling center, the lateral floor plate, a crucial step to create the burst of Shh required for OPC specification. At the same time, FGFs prevent down-regulation of Olig2 in pMN progenitor cells as these cells receive higher threshold of the Shh signal. Finally, we bring arguments favoring a key role of newly differentiated neurons acting as providers of the FGF signal required to trigger OPC generation in the ventral spinal cord. Conclusion Altogether our data reveal that the FGF signaling pathway is activated and required for OPC commitment in the ventral spinal cord. More generally, our data may prove important in defining strategies to produce large populations of determined oligodendrocyte precursor cells from undetermined neural progenitors, including stem cells. In the long run, these new data could be useful in attempts to stimulate the oligodendrocyte fate in residing neural stem cells
Additional file 2: Table S1. of Eph/Ephrin Signaling Controls Progenitor Identities In The Ventral Spinal Cord
Figure-by-figure details on sample size (DOCX 13 kb
Additional file 1: of Eph/Ephrin Signaling Controls Progenitor Identities In The Ventral Spinal Cord
Supplemental Code. (PDF 42 kb
Additional file 3: Figure S1–3. of Eph/Ephrin Signaling Controls Progenitor Identities In The Ventral Spinal Cord
Expression of Shh is not changed in ephrin mutants. (PDF 330 kb