Biology subjects

Despin-Guitard, E.

Publications and source records attributed to Despin-Guitard, E..

3 recordsLinked to original sources

bioRxiv2024

Occurrence of non-apical mitoses at the primitive streak, induced by relaxation of actomyosin and acceleration of the cell cycle, contributes to cell delamination during mouse gastrulation.

During the epithelial-mesenchymal transition driving mouse embryo gastrulation, cells at the primitive streak divide more frequently that in the rest of the epiblast, and half of those divisions happen away from the apical pole. These observations suggests that non-apical mitoses might play a role in cell delamination and/or mesoderm specification. We aimed to uncover and challenge the molecular determinants of mitosis position in the different regions of the epiblast through a combination of computational modeling and pharmacological treatments of embryos. Blocking basement membrane degradation at the streak had no impact on the asymmetry in mitosis frequency and position. By contrast disturbance of actomyosin cytoskeleton or cell cycle dynamics elicited ectopic non-apical mitosis and showed that the streak region is characterized by local relaxation of the actomyosin cytoskeleton and less stringent regulation of cell division. These factors are essential for normal dynamics at the streak but are not sufficient to promote acquisition of mesoderm identity or ectopic cell delamination in the epiblast. Exit from the epithelium requires additional events, such as detachment from the basement membrane. Altogether, our data indicate that cell delamination at the streak is a morphogenetic process which results from a cooperation between EMT events and the local occurrence of non-apical mitoses driven by specific cell cycle and contractility parameters.

developmental biology↗

bioRxiv2020

An asymmetry in the frequency and position of mitosis in the epiblast precedes gastrulation and suggests a role for mitotic rounding in cell delamination during primitive streak epithelial-mesenchymal transition.

The epiblast, a pseudostratified epithelium, is the precursor for the three main germ layers required for body shape and organogenesis: ectoderm, mesoderm, and endoderm. At gastrulation, a subpopulation of epiblast cells constitutes a transient posteriorly located structure called the primitive streak, where cells that undergo epithelial-mesenchymal transition make up the mesoderm and endoderm lineages. In order to observe the behavior of individual cells, epiblast cells were labeled ubiquitously or in a mosaic fashion using fluorescent membrane reporters. The cell shapes of individual cells and the packing and behaviour of neighbouring cells during primitive streak formation were recorded through live time-lapse imaging. Posterior epiblast displayed a higher frequency of rosettes, a signature of cell rearrangements, prior to primitive streak initiation. A third of rosettes were associated with a central cell undergoing mitosis. Interestingly, cells at the primitive streak, in particular delaminating cells, underwent mitosis twice more frequently than other epiblast cells, suggesting a role for cell division in epithelial-mesenchymal transition. Pseudostratified epithelia are characterized by interkinetic nuclear migration, where mitosis occurs at the apical side of the epithelium. However, we found that exclusively on the posterior side of the epiblast, mitosis was not restricted to the apical side. Non-apical mitosis was apparent as early as E5.75, just after the establishment of the anterior-posterior axis, and prior to initiation of epithelial-mesenchymal transition. Non-apical mitosis was associated with primitive streak morphogenesis, as it occurred specifically in the streak even when ectopically located. Most non-apical mitosis resulted in one or two daughter cells leaving the epiblast layer to become mesoderm. Furthermore, in contrast to what has been described in other pseudostratified epithelia such as neuroepithelium, the majority of cells dividing apically detached completely from the basal pole in the epiblast. Cell rearrangement associated with mitotic cell rounding in the posterior epiblast during gastrulation, in particular when it occurs on the basal side, might thus facilitate cell ingression through the PS and transition to a mesenchymal phenotype. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/959080v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@18530b2org.highwire.dtl.DTLVardef@1400a63org.highwire.dtl.DTLVardef@169f688org.highwire.dtl.DTLVardef@1b87931_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2019

Interkinetic nuclear movements promote apical expansion in pseudostratified epithelia at the expense of apicobasal elongation

Pseudostratified epithelia (PSE) are a common type of columnar epithelia found in a wealth of embryonic and adult tissues such as ectodermal placodes, the trachea, the ureter, the gut and the neuroepithelium. PSE are characterized by the choreographed displacement of cells nuclei along the apicobasal axis according to phases of their cell cycle. Such movements, called interkinetic movements (INM) have been proposed to influence tissue expansion and shape and suggested as culprit in several congenital diseases such as CAKUT and esophageal atresia. INM rely on cytoskeleton dynamics just as adhesion, contractility and mitosis do. Therefore, longer term impairment of INM without affecting proliferation and adhesion is currently technically unachievable. Here we bypassed this hurdle by generating a 2D agent-based model of a proliferating PSE and compared its output to the growth of the chick neuroepithelium to assess the interplay between INM and these other important cell processes during growth of a PSE. We found that INM directly generates apical expansion and apical nuclear crowding. In addition, our data strongly suggest that apicobasal elongation of cells is not an emerging property of a proliferative PSE but rather requires a specific elongation program. We then discuss how such program might functionally link INM, tissue growth and differentiation.\n\nAuthors SummaryPseudostratified epithelia (PSE) are a common type of epithelia characterized by the choreographed displacement of cells nuclei along the apicobasal axis during proliferation. These so-called interkinetic movements (INM) were proposed to influence tissue expansion and suggested as culprit in several congenital diseases. INM rely on cytoskeleton dynamics. Therefore, longer term impairment of INM without affecting proliferation and adhesion is currently technically unachievable. We bypassed this hurdle by generating a mathematical model of PSE and compared it to the growth of an epithelium of reference. Our data show that INM drive expansion of the apical domain of the epithelium and suggest that apicobasal elongation of cells is not an emerging property of a proliferative PSE but might rather requires a specific elongation program.

developmental biology↗