Cardiac development, pathophysiology and regeneration

     

    1) Role of Pitx2c in human atrial fibrilation

    2) Cardiac precursors cell fate during heart development 

    3) microRNAs and their role during cardiogenesis

   

 

     4) Long non-coding RNA and heart development

Skeletal muscle development, pathophysiology and regeneration

    1) Role of Pitx2c during skeletal muscle myogenesis and regeneration

 

   2) microRNAs as therapeutic tools for skeletal muscle repair

Figure 1. Morphological remodeling of adult atrial-specific Pitx2 conditional mutants (A). Transversal histological sections of adult ventricular NppaCre−Pitx2floxed/floxed (B) and NppaCre+Pitx2−/− (C) chambers illustrate a significant IVS thickness (double arrows). PITX2C qRT-PCR analysis in AF patients. D, PITX2C expression in right atrial biopsies from AF patients and no-AF patients. In 4 of 5 comparisons (80%), PITX2C expression is decreased approximately 80% to 90% in AF patients as compared with no-AF patients. E, PITX2C expression in left atrial biopsies from AF patients and no-AF patients. In 3 of 4 (75%) comparisons, PITX2C expression is similarly decreased (approximately 80% to 90%) in AF patients as compared with no-AF patients (see Chinchilla A et al, 2011).

Figure 2. Contribution of the posterior second heart field (pSHF) to the dorsal atria and sinus venosus. A, An example of double-dye labeling of the right (arrow) and left (arrowhead) sides at 6 somites (brightfield/fluorescence). B, Fluorescence image of a dorsal view of the heart from the embryo labeled in (A) after 40 hours of culture. The pSHF cell contribution is shown by labeling at the dorsal right (arrows) and left atrium (white arrowhead) and sinus venosus (black arrowhead). C, dorsal view after dye injection in the left pSHF showing labeling in the left sinus venosus (SV) and dorsal left atrium (LA) myocardium (myo). D, Transection of this heart (line in C) shows dye in the endocardium (endo; arrow) as well as in the myo. HT indicates heart tube; 20s, 6s, 20-, and 6-somite stage, respectively; OFT, outflow tract; DRA, dorsal side of the right atrium; AVC, atrioventricular canal; DLA, dorsal side of the left atrium (Dominguez JN et al, 2012).

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Figure 3. A-H: Representative microscopy images from AVC explant cultures incubated during 24 hr in control conditions (A,C, E and G) and after pre-miRNA-23b (D), pre-miR-199a (F), and anti-miRNA-23b transfection (H), respectively. B corresponds to a positive control of EMT inhibition resulting from pre-incubation with Glucose (Glu) 20 mM. Note that Glu 20 mM, miR-23b and miR-199a conditions display lower EMT spreading compared to control conditions (Bonet F et al, 2015).

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Figure 4. Analysis of Pitx2c−/− embryos: A: schematic representation of morphometric analyses in Pitx2c−/− mutant embryos (E12.5) carried out by evaluating limb length (black line; broken black line: proximal end of the limb) as well as limb and body areas (delineated by white broken line and blue line respectively) by using the image J software (NIH Image) in a total of 150 embryos (n = 40 for Pitx2c−/−, n = 70 for Pitx2c+/− and n = 40 for Pitx2+/+). B: Representative image of immunohistochemical Pax3 and Pax7 co-staining showing close up views of stained cells in Pitx2c−/−, Pitx2c+/− and wild type littermate embryos. Pax7 staining alone is also shown. C: Representative image of immunohistochemical co-staining for Pax3 and PHH3 as well as Pax7 and PHH3 co-staining showing close up views of stained cells in Pitx2c−/−, Pitx2c+/− and wild type littermates embryos. Although the analysis was performed in limbs and dermomyotome, only dermomyotomes are shown (Lozano-Velasco E et al, 2011). 

Figura 5. Tissue distribution of miR-15b, miR-23b, miR-106b, and miR-503 in limb muscles of C57BL/10 mice. miRNAs were expressed mostly in cells that presented a tissue distribution very similar to that of satellite cells, as illustrated by Pax7 costaining for miR-106b. An LNA probe with a scrambled sequence was used to test the specificity of the probes (Lozano-Velasco E et al, 2015) . 

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We are currently investigating the expression profile of distinct long non-coding RNAs during mouse and chicken cardiogenesis as well as how these lcnRNAs are regulated in normal and diseased conditions.