Biomedical subjects

François Giudicelli

Publications and source records attributed to François Giudicelli.

3 recordsLinked to original sources

PubMed2004

The vertebrate segmentation clock.

In vertebrate embryos, somite segmentation is controlled by a molecular clock, in the form of a transcriptional oscillator that operates in the presomitic mesoderm. Most of the genes implicated in the oscillator belong to the Notch pathway; a recently discovered exception is the Wnt pathway gene Axin2. Experiments have revealed several negative feedback loops that might generate oscillations, leading to at least four different theories. The simplest of these is based on direct autoinhibition of certain members of the hairy/E(spl) family of Notch target genes--Hes7 in the mouse, and her1 and her7 in the zebrafish. A mathematical account of this mechanism explains some surprising observations and suggests that the period of oscillation is chiefly determined by the transcriptional and translational delays--the times required to make a molecule of the mRNA and a molecule of the protein.

Animals↗

PubMed2003

Novel activities of Mafb underlie its dual role in hindbrain segmentation and regional specification.

The bZip transcription factor Mafb is expressed in two segments of the developing vertebrate hindbrain: the rhombomeres 5 and 6. Loss of Mafb expression in the mouse mutant kreisler leads to elimination of r5 and to alterations of r6 regional identity. Here, we further investigated the role of Mafb in hindbrain patterning using gain-of-function experiments in the chick embryo. Our work has revealed novel functions for Mafb, including a positive autoregulatory activity, the capacity to repress Hoxb1 expression, and the capacity to synergise with or antagonise Krox20 activity. These different activities appear to be spatially restricted in the hindbrain, presumably due to interactions with other factors. Reinvestigation of the kreisler mutation indicated that it also results in an ectopic activation of Mafb in rhombomere 3, accounting for the previously described molecular alterations of this rhombomere in the mutant. Together, these data allow us to refine our view of the dual function of Mafb in both segmentation and specification of anteroposterior identity in the hindbrain.

Animals↗

PubMed2002

Krox20 and kreisler co-operate in the transcriptional control of segmental expression of Hoxb3 in the developing hindbrain.

In the segmented vertebrate hindbrain, the Hoxa3 and Hoxb3 genes are expressed at high relative levels in the rhombomeres (r) 5 and 6, and 5, respectively. The single enhancer elements responsible for these activities have been identified previously and shown to constitute direct targets of the transcription factor kreisler, which is expressed in r5 and r6. Here, we have analysed the contribution of the transcription factor Krox20, present in r3 and r5. Genetic analyses demonstrated that Krox20 is required for activity of the Hoxb3 r5 enhancer, but not of the Hoxa3 r5/6 enhancer. Mutational analysis of the Hoxb3 r5 enhancer, together with ectopic expression experiments, revealed that Krox20 binds to the enhancer and synergizes with kreisler to promote Hoxb3 transcription, restricting enhancer activity to their domain of overlap, r5. These analyses also suggested contributions from an Ets-related factor and from putative factors likely to heterodimerize with kreisler. The integration of multiple independent inputs present in overlapping domains by a single enhancer is likely to constitute a general mechanism for the patterning of subterritories during vertebrate development.

Animals↗