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Acción del locus TH-insulina en la cardiogénesis

AuthorsMartínez-Campos, Enrique
AdvisorHernandez-Sanchez, Catalina; Martínez, Alberto
KeywordsDesarrollo cardiaco
tirosina hidroxilasa
Issue Date22-Feb-2012
PublisherCSIC - Centro de Investigaciones Biológicas (CIB)
Universidad Autónoma de Madrid
AbstractTyrosine hydroxylase (TH) and insulin are well-characterized independent genes that are situated in tandem, a syntenic organization that can be traced to the early metazoans. Whereas the roles of these proteins postnatally are well known, the presence and function of the TH-insulin locus in organogenesis is unclear. The aim of this study was to define the expression of Th and insulin genes during cardiac development and to unravel their role in heart formation. Th expression and activity was analyzed in early chick cardiogenesis. Addition of dopamine induced ectopic expression of Bmp-2, linking TH to early cardiac differentiation programmes. Overexpression of Th led to increased atrial myosin heavy chain (AMHC-1) and T-box 5 gene (TBX5) expression in the anterior region of the cardiac tube and induced bradyarrhythmia. Exposure to retinoic acid induced the expression of Th in parallel to that of Amhc-1 and Tbx5. Concordantly, inhibition of endogenous retinoic acid synthesis decreased the expression of Th as well as that of Amhc-1 and Tbx5. Insulin levels were also strictly regulated during cardiac development. The expression of two embryonic mRNA isoforms of insulin, Pro1B and Pro1B1, that differ from the pancreatic transcript was characterized on the embryonic cardiac tube, being the Pro1B1 the predominant isoform after the linear tube formation. Overexpression of the translationally active proinsulin embryonic transcript, Pro1B, and even more of the pancreatic transcript, Pro1A, caused cardiac malformations. Overexpression of Pro1B led to the reduction of Amhc-1 and Tbx5 expression. Moreover, expansion of Vmhc-1 expression into the posterior region of the cardiac tube was detected. Thus, TH and insulin are expressed in a dynamic pattern during the primitive heart tube formation. This locus is involved in the network of signals that drive early cardiac chamber specification, acting as a key regulators of the embryonic chick heart morphogenesis.
Description198 p.-34 fig.-4 tab.
Appears in Collections:(CIB) Tesis
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