Biomedical subjects

O Pourquie

Publications and source records attributed to O Pourquie.

5 recordsLinked to original sources

PubMed2003

Periodic notch inhibition by lunatic fringe underlies the chick segmentation clock.

The segmented aspect of the vertebrate body plan first arises through the sequential formation of somites. The periodicity of somitogenesis is thought to be regulated by a molecular oscillator, the segmentation clock, which functions in presomitic mesoderm cells. This oscillator controls the periodic expression of 'cyclic genes', which are all related to the Notch pathway. The mechanism underlying this oscillator is not understood. Here we show that the protein product of the cyclic gene lunatic fringe (Lfng), which encodes a glycosyltransferase that can modify Notch activity, oscillates in the chick presomitic mesoderm. Overexpressing Lfng in the paraxial mesoderm abolishes the expression of cyclic genes including endogenous Lfng and leads to defects in segmentation. This effect on cyclic genes phenocopies inhibition of Notch signalling in the presomitic mesoderm. We therefore propose that Lfng establishes a negative feedback loop that implements periodic inhibition of Notch, which in turn controls the rhythmic expression of cyclic genes in the chick presomitic mesoderm. This feedback loop provides a molecular basis for the oscillator underlying the avian segmentation clock.

Animals↗

PubMed1993

Identification in the chicken of GRL1 and GRL2: two granule proteins expressed on the surface of activated leukocytes.

We report the production of two monoclonal antibodies reacting, respectively, with a 92-kDa protein (GRL1) and a 40- to 65-kDa membrane glycoprotein (GRL2), both present in chicken thrombocyte and myelocyte granules. We examined the expression of GRL1 and GRL2 during the development of the hematopoietic system: GRL1 is restricted to thrombocytes and myelocytes, whereas GRL2 is present in thrombocytes, myelocytes, myeloid progenitors, and a subpopulation of erythroid progenitors. In the lymphoid lineages, neither GRL1 nor GRL2 is expressed during thymus and bursa ontogeny or on resting peripheral blood lymphocytes. However, CD3+ T lymphoblasts obtained by mitogenic stimulation of GRL2-negative quiescent T lymphocytes are stained on their surface by anti-GRL2 Mab. In vitro stimulation of thrombocytes and granulocytes with their specific secretagogues results in the expression of GRL1 and in the overexpression of GRL2 on the cell surface. These observations are consistent with the following two conclusions: the presence on the cell surface of GRL1 epitope is a marker of thrombocyte and myelocyte activation; GRL2 epitope is present on the granule membrane of leukocytes, including T cells. In that respect, GRL2 appears to share certain features with leukocyte activation antigens recently described in human.

Animals↗

PubMed1992

An antigen expressed by avian neuronal cells is also expressed by activated T lymphocytes.

A monoclonal antibody, anti-BEN, initially characterized by its reactivity with an epitope present on the surface of avian bursa epithelial cells and neurons, also reacts with membrane molecules on some hemopoietic cells. In this study we examine BEN expression on lymphoid cells in thymus, spleen, and blood. We demonstrate that BEN is an activation antigen on mature T lymphocytes. It is not expressed on peripheral blood or splenic lymphocytes, but following mitogenic or allogeneic stimulation of blood lymphocytes it appears rapidly on a T cell subpopulation in parallel with the appearance of IL-2 receptors. BEN is also expressed on III-C5 cells, an avian IL-2-dependent permanent T cell line, and on immature CD4+CD8+ thymocytes. BEN is not expressed by resting or actively proliferating B cells. Biochemical analyses of the BEN protein on T lymphoblasts shows that the molecule is similar in size to the BEN molecules on bursa epithelial cells and on neurons. The physicochemical properties of the BEN protein and its tissue distribution differs from other known avian and mammalian T cell activation markers, differentiation antigens, and integrins. Thus BEN is a novel marker of activated T cells in birds.

Animals↗

PubMed1992

BEN, a novel surface molecule of the immunoglobulin superfamily on avian hemopoietic progenitor cells shared with neural cells.

BEN is a novel molecule of the immunoglobulin superfamily that we previously identified by means of a monoclonal antibody on neural cell populations during avian development and epithelial cells of the bursa of Fabricius. In this paper, we describe the expression of BEN by hemopoietic cells during ontogeny. In the thymus, BEN is expressed as early as E9, and from E12 until just after hatching 30-60% of thymocytes are BEN positive. Thus the cells expressing BEN are immature thymocytes and not yet differentiated T cells. In the spleen, BEN expression parallels the myelopoietic activity. It is present on 75% of splenocytes during embryonic development and falls rapidly to 20% of cells during the first week after hatching when the spleen is becoming a secondary lymphoid organ. BEN is also found on a large proportion (about 80% positive cells) of bone marrow cells during ontogeny. Post hatching, BEN is present on 40-50% of bone marrow cells. The population of BEN-positive cells in the bone marrow includes myeloid and erythroid progenitor cells, identified by their ability to form colonies in vitro. BEN expression is lost as progenitor cells proliferate and differentiate to develop mature colonies in the clonal assay. Mature myeloid cells, such as macrophages, granulocytes, thrombocytes, and erythrocytes do not express the BEN antigen. Taken together, these data demonstrated that BEN is a stage-specific rather than a lineage-specific differentiation antigen expressed by immature hemopoietic cells.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMedDate not supplied

The vertebrate segmentation clock.

Vertebrate somitogenesis has been shown to be associated with a molecular oscillator, the segmentation clock, whose periodicity matches that of the process of somitogenesis. The existence of such a clock in presomitic mesoderm (PSM) cells was originally proposed in theoretical models such as the 'clock and wavefront'. Molecular evidence for the existence of this clock in vertebrates has been obtained on the basis of the periodic expression of several genes, most of which are related to the Notch signalling pathway. These genes are expressed in a dynamic sequence which appears as a wave sweeping caudo-rostrally along the whole PSM once during each somite formation. Notch-pathway mouse and fish mutants lose the dynamic expression of the cycling genes, indicating that Notch signalling is required for their periodic expression, or is required to coordinate the oscillations between PSM cells. Therefore Notch signalling is either part of the mechanism of the oscillator itself or acts as a cofactor required for cycling gene expression. A further potentially important role for the segmentation clock is to periodically activate Notch signalling in the rostral presomitic mesoderm, thereby generating the periodic formation of somite boundaries.

Animals↗