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Olivier Pourquié

Publications and source records attributed to Olivier Pourquié.

At least 19 recordsLinked to original sources
PubMed2006

A complex oscillating network of signaling genes underlies the mouse segmentation clock.

The segmental pattern of the spine is established early in development, when the vertebral precursors, the somites, are rhythmically produced from the presomitic mesoderm. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the oscillator associated with this process, the segmentation clock, drives the periodic expression of a large network of cyclic genes involved in cell signaling. Mutually exclusive activation of the notch-fibroblast growth factor and Wnt pathways during each cycle suggests that coordinated regulation of these three pathways underlies the clock oscillator.

Algorithms↗
PubMed2006

On periodicity and directionality of somitogenesis.

It is currently thought that the mechanism underlying somitogenesis is linked to a molecular oscillator, the segmentation clock, and to gradients of signaling molecules within the paraxial mesoderm. Here, we review the current picture of this segmentation clock and gradients, and use this knowledge to critically ask: What is the basis for periodicity and directionality of somitogenesis?

Animals↗
PubMed2006

Collinear activation of Hoxb genes during gastrulation is linked to mesoderm cell ingression.

The vertebral column exhibits segmentation and regionalization along the antero-posterior axis. During embryogenesis, the rhythmic production of the precursors of the vertebrae, the somites, imposes a segmented aspect to the spine, whereas the spine's regional differentiation is controlled by Hox genes. Here we show that in the paraxial mesoderm, Hoxb genes are first activated in a temporal collinear fashion in precursors located in the epiblast lateral to the primitive streak. Our data suggest that collinear activation of Hoxb genes regulates the flux of cells from the epiblast to the streak and thus directly controls the establishment of the genes' characteristic nested expression domains in the somites. This suggests that establishment of the spatial co-linearity in the embryo is directly controlled by the Hox genes themselves.

Animals↗
PubMed2006

Oscillations of the snail genes in the presomitic mesoderm coordinate segmental patterning and morphogenesis in vertebrate somitogenesis.

The segmented body plan of vertebrate embryos arises through segmentation of the paraxial mesoderm to form somites. The tight temporal and spatial control underlying this process of somitogenesis is regulated by the segmentation clock and the FGF signaling wavefront. Here, we report the cyclic mRNA expression of Snail 1 and Snail 2 in the mouse and chick presomitic mesoderm (PSM), respectively. Whereas Snail genes' oscillations are independent of NOTCH signaling, we show that they require WNT and FGF signaling. Overexpressing Snail 2 in the chick embryo prevents cyclic Lfng and Meso 1 expression in the PSM and disrupts somite formation. Moreover, cells mis-expressing Snail 2 fail to express Paraxis, remain mesenchymal, and are thereby inhibited from undergoing the epithelialization event that culminates in the formation of the epithelial somite. Thus, Snail genes define a class of cyclic genes that coordinate segmentation and PSM morphogenesis.

Animals↗
PubMed2005

In vivo analysis of mRNA stability using the Tet-Off system in the chicken embryo.

The rate of mRNA degradation plays an important role in the control of gene expression. The mRNA stability is mainly dependent on cis-regulatory elements contained in the 3' or 5' untranslated region (UTR) of the mature mRNAs, and its regulation is an efficient way to adapt the level of a given transcript in the cell. Although this process has been well studied in cell culture, little is known about mRNA stability during embryonic development. Here, we describe an assay that combines the tetracyclin-dependent inducible system Tet-Off with in ovo electroporation to monitor mRNA stability in the chick neural tube. We show, by using the GFP intensity as an indirect reporter system, that the 3'UTR of Lunatic Fringe strongly destabilizes transcripts, while transcripts bearing the 3'UTR of Fgf8 are much more stable. This simple assay provides a powerful tool to study mRNA dynamics in vivo.

3' Untranslated Regions↗
PubMed2005

Control of the segmentation process by graded MAPK/ERK activation in the chick embryo.

The regular spacing of somites during vertebrate embryogenesis involves a dynamic gradient of FGF signaling that controls the timing of maturation of cells in the presomitic mesoderm (PSM). How the FGF signal is transduced by PSM cells is unclear. Here, we first show that the FGF gradient is translated into graded activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway along the PSM in the chicken embryo. Using in ovo electroporation of PSM cells, we demonstrate that constitutive activation of ERK signaling in the PSM blocks segmentation by preventing maturation of PSM cells, thus phenocopying the overexpression of FGF8. Conversely, inhibition of ERK phosphorylation mimics a loss of function of FGF signaling in the PSM. Interestingly, video microscopy analysis of cell movements shows that ERK regulates the motility of PSM cells, suggesting that the decrease of cell movements along the PSM enables mesenchymal PSM cells to undergo proper segmentation. Together, our data demonstrate that ERK is the effector of the gradient of FGF in the PSM that controls the segmentation process.

Animals↗
PubMed2005

Retinoic acid coordinates somitogenesis and left-right patterning in vertebrate embryos.

A striking feature of the body plan of a majority of animals is bilateral symmetry. Almost nothing is known about the mechanisms controlling the symmetrical arrangement of the left and right body sides during development. Here we report that blocking the production of retinoic acid (RA) in chicken embryos leads to a desynchronization of somite formation between the two embryonic sides, demonstrated by a shortened left segmented region. This defect is linked to a loss of coordination of the segmentation clock oscillations. The lateralization of this defect led us to investigate the relation between somitogenesis and the left-right asymmetry machinery in RA-deficient embryos. Reversal of the situs in chick or mouse embryos lacking RA results in a reversal of the somitogenesis laterality defect. Our data indicate that RA is important in buffering the lateralizing influence of the left-right machinery, thus permitting synchronization of the development of the two embryonic sides.

Aldehyde Oxidoreductases↗
PubMed2005

Chicken genome: new tools and concepts.

Last spring, the Second International Chicken Genome Workshop was held at the Stowers Institute for Medical Research, less than 2 months after the first draft of the chicken genome was publicly released in March, 2004. This major event was highly anticipated by the chicken community, because of the invaluable resources that would be newly provided. In addition, from an evolutionary standpoint, birds are the species most closely related to mammals, whose genome has been sequenced. The meeting gathered both agricultural and academic chicken communities and provided the opportunity to discuss the status of the chicken genome sequencing, the preliminary analysis of the chicken genome sequences freshly available, and the impact on avian genetic tools.

Animals↗
PubMed2005

Synchronised cycling gene oscillations in presomitic mesoderm cells require cell-cell contact.

Segmentation of the vertebrate body axis is initiated early in development with the sequential formation of somites. Somitogenesis is temporally regulated by a molecular oscillator, the segmentation clock, which acts within presomitic mesoderm (PSM) cells to drive periodic expression of the cyclic genes. We have investigated the kinetics of the progression of cycling gene expression along the PSM. Here we show that c-hairy1 and c-hairy2 mRNA expression traverses the PSM in an entirely progressive manner and that both these genes and c-Lfng maintain a similar anterior limit of expression during each cycle. However, some differences are seen regarding both the onset of a new oscillation of these genes and the duration of their expression in the caudal PSM. We also investigated whether oscillating cyclic gene expression in the PSM is entirely cell autonomous. We find that while small PSM explants are still able to maintain their oscillation schedule, once they are dissociated, PSM cells are no longer able to maintain synchronous oscillations. The results imply that cell communication or a community effect is essential for the normal pattern of cyclic gene expression in these cells.

Animals↗
PubMed2004

fgf8 mRNA decay establishes a gradient that couples axial elongation to patterning in the vertebrate embryo.

Formation and patterning of the vertebrate embryo occur in a head-to-tail sequence. This progressive mode of body formation from the posterior end of the embryo requires a strict temporal coordination of tissue differentiation--a process involving fibroblast growth factor (FGF) signalling. Here we show that transcription of fgf8 messenger RNA is restricted to the growing posterior tip of the embryo. fgf8 mRNA is progressively degraded in the newly formed tissues, resulting in the formation of an mRNA gradient in the posterior part of the embryo. This fgf8 mRNA gradient is translated into a gradient of FGF8 protein, which correlates with graded phosphorylation of the kinase Akt, a downstream effector of FGF signalling. Such a mechanism provides an efficient means to monitor the timing of FGF signalling, coupling the differentiation of embryonic tissues to the posterior elongation of the embryo. In addition, this mechanism provides a novel model for morphogen gradient formation.

Animals↗
PubMed2004

Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1.

The immunoglobulin superfamily adhesion molecule BEN (other names include ALCAM, SC1, DM-GRASP, neurolin, and CD166) has been implicated in the control of numerous developmental and pathological processes, including the guidance of retinal and motor axons to their targets. To test hypotheses about BEN function, we disrupted its gene via homologous recombination and analyzed the resulting mutant mice. Mice lacking BEN are viable and fertile, and display no external morphological defects. Despite grossly normal trajectories, both motor and retinal ganglion cell axons fasciculated poorly and were occasionally misdirected. In addition, BEN mutant retinae exhibited evaginated or invaginated regions with photoreceptor ectopias that resembled the "retinal folds" observed in some human retinopathies. Together, these results demonstrate that BEN promotes fasciculation of multiple axonal populations and uncover an unexpected function for BEN in retinal histogenesis.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2004

The chick embryo: a leading model in somitogenesis studies.

The vertebrate body is built on a metameric organization which consists of a repetition of functionally equivalent units, each comprising a vertebra, its associated muscles, peripheral nerves and blood vessels. This periodic pattern is established during embryogenesis by the somitogenesis process. Somites are generated in a rhythmic fashion from the presomitic mesoderm and they subsequently differentiate to give rise to the vertebrae and skeletal muscles of the body. Somitogenesis has been very actively studied in the chick embryo since the 19th century and many of the landmark experiments that led to our current understanding of the vertebrate segmentation process have been performed in this organism. Somite formation involves an oscillator, the segmentation clock whose periodic signal is converted into the periodic array of somite boundaries by a spacing mechanism relying on a traveling threshold of FGF signaling regressing in concert with body axis extension.

Animals↗
PubMed2004

Coupling segmentation to axis formation.

A characteristic feature of the vertebrate body is its segmentation along the anteroposterior axis, as illustrated by the repetition of vertebrae that form the vertebral column. The vertebrae and their associated muscles derive from metameric structures of mesodermal origin, the somites. The segmentation of the body is established by somitogenesis, during which somites form sequentially in a rhythmic fashion from the presomitic mesoderm. This review highlights recent findings that show how dynamic gradients of morphogens and retinoic acid, coupled to a molecular oscillator, drive the formation of somites and link somitogenesis to the elongation of the anteroposterior axis.

Animals↗
PubMed2003

The segmentation clock: converting embryonic time into spatial pattern.

In most animal species, the anteroposterior body axis is generated by the formation of repeated structures called segments. In vertebrate segmentation, a specialized mesodermal structure called the somite gives rise to skeletal muscles, vertebrae, and some dermis. Formation of the somites is a rhythmic process that involves an oscillator--the segmentation clock--driven by Wnt and Notch signaling. The clock ticks in somite precursors and halts when they reach a specific maturation stage defined as the wavefront, established by fibroblast growth factor and Wnt signaling. This process converts the temporal oscillations into the periodic spatial pattern of somite boundaries. The study of somite development provides insights into the spatiotemporal integration of signaling systems in the vertebrate embryo.

Animals↗
PubMed2003

Synthesis of new 3-alkoxy-7-amino-4-chloro-isocoumarin derivatives as new beta-amyloid peptide production inhibitors and their activities on various classes of protease.

A series of new 7-substituted-4-chloro-3-alkoxy isocoumarin derivatives were synthesized and evaluated as inhibitors of representative classes of proteases: serine protease (alpha-chymotrypsin, trypsin), cysteine protease (Caspase-3), and aspartyl protease (HIV-protease), 20S proteasome and also as inhibitors of amyloid peptide gamma-secretase-mediated production. Protease inhibition selectivity is directly related to the structure of the substituent at the 7-position of the isocoumarin nucleus. 7-Nitro-isocoumarin derivatives (4c, 4d, 4f) are potent alpha-chymotrypsin inhibitors but slightly active or inactive on HIV-protease, as well as on cysteine protease. In contrast, only derivatives bearing a free amino (5d, 5f) or a substituted amino group (6f) at the 7-position of the isocoumarin nucleus, were found weakly active or inactive on alpha-chymotrypsin, trypsin, Caspase-3 and HIV-protease, but prevent gamma-secretase-mediated production of Abeta 40/42 amyloid peptides, which is known to be involved in Alzheimer's disease. Moreover, the most active compounds on beta-amyloid peptide production [JLK6 (5d), JLK2 (5f) and JLK7 (6f)] show only weak or moderate inhibitory activity on the 20S proteasome. The obtained results suggest that the described new isocoumarin analogues could be of interest, since compounds like JLK6 (5d), JLK2 (5f) and JLK7 (6f) can be considered as possible hits for the development of new agents directed towards Alzheimer's disease.

Amyloid Precursor Protein Secretases↗
PubMed2003

Entrails, heart, brain, limbs, and lymphatics- a recipe for success?

A recent Juan March Foundation workshop entitled Developmental Mechanisms in Vertebrate Organogenesis brought 50 developmental biologists together in Madrid to share some of their latest findings. Discussion topics included ectodermal organs such as the central nervous system (CNS) and skin, mesodermal organs such as the heart, limb, vasculature, and kidney, and endodermal organs such as the pancreas and liver. Discussions extended into the late hours of the night as the meeting participants indulged in tasting some of their favorite organs, in the form of Spanish delicacies.

Animals↗