Biomedical subjects

Julien Dubrulle

Publications and source records attributed to Julien Dubrulle.

6 recordsLinked to original sources

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↗

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

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

Welcome to syndetome: a new somitic compartment.

Virtually nothing was known about the embryonic origin of tendons, until a recent paper by Brent and colleagues in which they track the origin of tendon progenitors of the body axis and reveal the molecular events and tissue interactions leading to their commitment.

Cell Differentiation↗

PubMed2002

From head to tail: links between the segmentation clock and antero-posterior patterning of the embryo.

Periodic production of somites along the anteroposterior axis of the vertebrate body involves a molecular oscillator, the 'segmentation clock', which can be visualized through the periodic activation of genes linked to the Notch pathway. Recent findings show that oscillations initiate at gastrula stages and point to a role for FGF signaling in positioning the segmental boundaries. This clock also controls aspects of spatio-temporal Hox gene activation thus ensuring a perfect match between segment boundary position and future regional identity of the somites.

Animals↗