Biomedical subjects

Françoise Trousse

Publications and source records attributed to Françoise Trousse.

5 recordsLinked to original sources

PubMed2007

Neurogenic role of Gcm transcription factors is conserved in chicken spinal cord.

Although glial cells missing (gcm) genes are known as glial determinants in the fly embryo, the role of vertebrate orthologs in the central nervous system is still under debate. Here we show for the first time that the chicken ortholog of fly gcm (herein referred to as c-Gcm1), is expressed in early neuronal lineages of the developing spinal cord and is required for neural progenitors to differentiate as neurons. Moreover, c-Gcm1 overexpression is sufficient to trigger cell cycle exit and neuronal differentiation in neural progenitors. Thus, c-Gcm1 expression constitutes a crucial step in the developmental cascade that prompts progenitors to generate neurons: c-Gcm1 acts downstream of proneural (neurogenin) and progenitor (Sox1-3) factors and upstream of NeuroM neuronal differentiation factor. Strikingly, this neurogenic role is not specific to the vertebrate gene, as fly gcm and gcm2 are also sufficient to induce the expression of neuronal markers. Interestingly, the neurogenic role is restricted to post-embryonic stages and we identify two novel brain neuronal lineages expressing and requiring gcm genes. Finally, we show that fly gcm and the chick and mouse orthologs induce expression of neural markers in HeLa cells. These data, which demonstrate a conserved neurogenic role for Gcm transcription factors, call for a re-evaluation of the mode of action of these genes during evolution.

Animals↗

PubMed2006

Proper patterning of the optic fissure requires the sequential activity of BMP7 and SHH.

The optic disc develops at the interface between optic stalk and retina, and enables both the exit of visual fibres and the entrance of mesenchymal cells that will form the hyaloid artery. In spite of the importance of the optic disc for eye function, little is known about the mechanisms that control its development. Here, we show that in mouse embryos, retinal fissure precursors can be recognised by the expression of netrin 1 and the overlapping distribution of both optic stalk (Pax2, Vax1) and ventral neural retina markers (Vax2, Raldh3). We also show that in the absence of Bmp7, fissure formation is not initiated. This absence is associated with a reduced cell proliferation and apoptosis in the proximoventral quadrant of the optic cup, lack of the hyaloid artery, optic nerve aplasia, and intra-retinal misrouting of RGC axons. BMP7 addition to organotypic cultures of optic vesicles from Bmp7-/- embryos rescues Pax2 expression in the ventral region, while follistatin, a BMP7 antagonist, prevents it in early, but not in late, optic vesicle cultures from wild-type embryos. The presence of Pax2-positive cells in late optic cup is instead abolished by interfering with Shh signalling. Furthermore, SHH addition re-establishes Pax2 expression in late optic cups derived from ocular retardation (or) embryos, where optic disc development is impaired owing to the near absence of SHH-producing RGC. Collectively, these data indicate that BMP7 is required for retinal fissure formation and that its activity is needed, before SHH signalling, for the generation of PAX2-positive cells at the optic disc.

Aldehyde Oxidoreductases↗

PubMed2005

SFRP1 regulates the growth of retinal ganglion cell axons through the Fz2 receptor.

Axon growth is governed by the ability of growth cones to interpret attractive and repulsive guidance cues. Recent studies have shown that secreted signaling molecules known as morphogens can also act as axon guidance cues. Of the large family of Wnt signaling components, only Wnt4 and Wnt5 seem to participate directly in axon guidance. Here we show that secreted Frizzled-related protein 1 (SFRP1), a proposed Wnt signaling inhibitor, can directly modify and reorient the growth of chick and Xenopus laevis retinal ganglion cell axons. This activity does not require Wnt inhibition and is modulated by extracellular matrix molecules. Intracellularly, SFRP1 function requires G(alpha) protein activation, protein synthesis and degradation, and it is modulated by cyclic nucleotide levels. Because SFRP1 interacts with Frizzled-2 (Fz2) and interference with Fz2 expression abolishes growth cone responses to SFRP1, we propose a previously unknown function for this molecule: the ability to guide growth cone movement via the Fz2 receptor.

Animals↗

PubMed2004

Morphogens as growth cone signalling molecules.

Morphogen signalling among cells is one of the most important mechanisms underlying the progressive patterning of embryos. Members of the hedgehog (Hh), wingless (Wnt), transforming growth factor-beta (TGFbeta), and fibroblast growth factor (Fgf) families of extracellular signalling molecules act as morphogens. Recent studies have demonstrated that members of these four families of proteins, secreted by well-characterised organiser centres in the central nervous system (CNS) as floor plate or midbrain-hindbrain boundary, are reused at later developmental stages to control axon growth. Here, we have summarised the evidence for this novel idea with a particular emphasis on those related to Shh and Wnt signalling-the object of some works in our laboratory.

Animals↗

PubMed2003

SFRP1 modulates retina cell differentiation through a beta-catenin-independent mechanism.

Secreted frizzled related proteins (SFRPs) are soluble molecules capable of binding WNTS and preventing the activation of their canonical signalling cascade. Here we show that Sfrp1 contributes to chick retina differentiation with a mechanism that does not involve modifications in the transcriptional activity of beta-catenin. Thus, addition of SFRP1 to dissociated retinal cultures or retroviral mediated overexpression of the molecule consistently promoted retinal ganglion and cone photoreceptor cell generation, while decreasing the number of amacrine cells. Measure of the activity of the beta-catenin-responsive Tcf-binding site coupled to a luciferase reporter in transiently transfected retinal cells showed that Sfrp1 was unable to modify the basal beta-catenin transcriptional activity of the retina cells. Interestingly, a dominant-negative form of GSK3beta gave similar results to those of Sfrp1, and a phosphorylation-dependent inhibition of GSK3beta activity followed SFRP1 treatment of retina cells. Furthermore, retroviral mediated expression of a dominant-negative form of GSK3beta induced a retina phenotype similar to that observed after Sfrp1 overexpression, suggesting a possible involvement of this kinase in SFRP1 function.

Amacrine Cells↗