miRNA Expression in Control and FSHD Fetal Human Muscle Biopsies

International audienceBackground :Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development. Methods :Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays. Results :During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD. Conclusions :This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated

Preparedness actions towards seismic risk mitigation for the general public in Martinique, French Lesser Antilles: a mid-term appraisal

International audienceMartinique is a French island in the Lesser Antilles, with a high seismic hazard. In 2006, Martinican stakeholders involved in seismic safety formed the "Réplik" working group ("Aftershock" in French), the first of its kind in this region. This paper addresses a mid-term appraisal of the first seismic awareness campaign organized by Réplik from 2006 to 2011, and how it has modified, or not, local earthquake and tsunami preparedness. Despite efforts from Réplik to assess its efficiency through surveys, a growing gap is noted between the observed awareness and the actual preparedness of the public. As usual, gender, age, educational level, then boredom and saturation contribute to this discrepancy; strong cultural items may also influence the perception of actions. To remain efficient and respond to public's expectations, Réplik must redirect its actions towards a cultural congruence of information: consideration of religion and local beliefs, comprehensive messages on TV and radio, use of Creole language, participatory experiences and drills, with a little bit of science. So that, the Réplik stakeholders can hope to increase Martinicans' involvement into the preparedness process, to cope quickly with a strong earthquake and this know-how can be shared with other seismically active islands in the Caribbean

microRNAs exclusively expressed in FSHD biopsies.

<p>microRNAs exclusively expressed in FSHD biopsies.</p

Summary of differentially expressed miRNAs.

<p>Contr: age-matched control biopsies</p><p>Summary of differentially expressed miRNAs.</p

Predicted common targets of miRNAs expressed exclusively in FSHD1.

<p>Five different algorithms were used to identify the predicted targets for miRs exclusively expressed in FSHD1 biopsies, and only the target-genes predicted in at least 3 of them were considered as probable target. In gray, miRNAs exclusively expressed in FSHD1 fetal muscle biopsies and in white, target genes of these FSHD1 miRNAs.</p

Venn-diagram showing the number of miRNAs modulated in FSHD1 fetuses at different stages of development.

<p>52 miRNAs were differentially expressed in the FSHD1 fetus at 14 weeks of development carrying 4.5 D4Z4 repeat units (FSHD 14.1), while 38 microRNAs were modulated in the FSHD1 fetus at 14 weeks of development with 1.5 D4Z4 repeat units (FSHD 14.2). These two fetuses at the same stage share 11 modulated miRNAs. 15 miRNAs were modulated in the FSHD1 fetus at 15 weeks of development, while at 22 weeks of development, we observed 35 differentially expressed miRNAs in FSHD1.</p

microRNAs exclusively expressed in FSHD biopsies.

<p>microRNAs exclusively expressed in FSHD biopsies.</p

Expression of myomiR in fetal muscle biopsies from FSHD1 are similar to fetal control muscle biopsies.

<p>Age-matched pair-wise comparison of myomiRs expression in FSHD1 (D) and healthy control biopsies (C) at 14, 15 and 22 weeks of development.</p

Overrepresented gene ontology-related biological processes in FSHD muscle.

<p>Graphical representation of the selected enriched biological processes (BP) from the list of putative target-genes based on Gene Ontology annotation. Dark bars: expected count of putative target-genes in each BP; light bars: observed BP enrichment; and, values alongside the bars. The overrepresentation was assessed with a statistical score based on a hypergeometric tests with p-values ≤ 0.001.</p

Distinctive patterns of miRNAs expression in human muscular development.

<p>Global miRNA expression profiling was performed using control muscle biopsies at 14, 15, 16, 18, 20, 22, 26 and 33 weeks of development. Stg2 (Stage 2, biopsies at 14–16 weeks of development) corresponds to secondary muscle fiber formation; trans (biopsies at 18 and 20 weeks of development) is the transition phase between the secondary myogenesis and the maturation phase; and, Stg3 3 (Stage 3, biopsies at 22–33 weeks of development) corresponds to the maturation phase. A- down-regulated microRNAs during development; B- up-regulated microRNAs during development (* P<0.05; nonparametric one-way ANOVA with 1,000 permutations; compared Stg2 with Stg3).</p