SummaryWnt signaling is a key regulator of vertebrate heart development; however, specific roles for human cardiomyocyte development remain uncertain. Here we use human embryonic stem cells (hESCs) to analyze systematically in human cardiomyocyte development the expression of endogenous Wnt signaling components, monitor pathway activity, and dissect stage-specific requirements for canonical and noncanonical Wnt signaling mechanisms using small-molecule inhibitors. Our analysis suggests that WNT3 and WNT8A, via FZD7 and canonical signaling, regulate BRACHYURY expression and mesoderm induction; that WNT5A/5B, via ROR2 and noncanonical signaling, regulate MESP1 expression and cardiovascular development; and that later in development WNT2, WNT5A/5B, and WNT11, via FZD4 and FZD6, regulate functional cardiomyocyte differentiation via noncanonical Wnt signaling. Our findings confirm in human development previously proposed roles for canonical Wnt signaling in sequential stages of vertebrate cardiomyogenesis, and identify more precise roles for noncanonical signaling and for individual Wnt signal and Wnt receptor genes in human cardiomyocyte development.

Developmental defects affecting the heart and aortic arch arteries are a significant phenotype observed in individuals with 22q11 deletion syndrome and are caused by a microdeletion on chromosome 22q11. TBX1, one of the deleted genes, is expressed throughout the pharyngeal arches and is considered a key gene, when mutated, for the arch artery defects. Pax9 is expressed in the pharyngeal endoderm and is downregulated in Tbx1 mutant mice. We show here that Pax9-deficient mice are born with complex cardiovascular malformations that affect the outflow tract and aortic arch arteries with failure of the 3rd and 4th pharyngeal arch arteries to form correctly. Transcriptome analysis indicated that Pax9 and Tbx1 may function together, and mice double heterozygous for Tbx1/Pax9 presented with a significantly increased incidence of interrupted aortic arch when compared with Tbx1 heterozygous mice. Using a novel Pax9Cre allele, we demonstrated that the site of this Tbx1-Pax9 genetic interaction is the pharyngeal endoderm, therefore revealing that a Tbx1-Pax9-controlled signalling mechanism emanating from the pharyngeal endoderm is required for crucial tissue interactions during normal morphogenesis of the pharyngeal arch artery system.

No abstract

Conventional medical treatments of Parkinson's disease (PD) are effective on motor disturbances but may have little impact on nonmotor symptoms, especially psychiatric ones. Thus, even when motor symptomatology improves, patients might experience deterioration in their quality of life. We have shown that 3 years of active theatre is a valid complementary intervention for PD as it significantly improves the well-being of patients in comparison to patients undergoing conventional physiotherapy. Our aim was to replicate these findings while improving the efficacy of the treatment. We ran a single-blinded pilot study lasting 15 months on 24 subjects with moderate idiopathic PD. 12 were assigned to a theatre program in which patients underwent “emotional” training. The other 12 underwent group physiotherapy. Patients were evaluated at the beginning and at the end of their treatments, using a battery of eight clinical and five neuropsychological scales. We found that the emotional theatre training improved the emotional well-being of patients, whereas physiotherapy did not. Interestingly, neither of the groups showed improvements in either motor symptoms or cognitive abilities tested by the neuropsychological battery. We confirmed that theatre therapy might be helpful in improving emotional well-being in PD.

No abstract