Genetic Control of Heart Function and Aging in Drosophila

Abstract

Why is Drosophila a good model of cardiac physiology?The fly heart has been an excellent model of cardiovascular development for over a decade. Since the discovery of the homeobox transcription factor tinman (Azpiazu and Frasch 1993, Bodmer 1993, Bodmer et al. 1990) and the recognition that it is conserved in vertebrates [reviewed in (Bodmer 1995, Harvey 1996], more and more evidence has corroborated the idea that much of the regulatory genetic network controlling the specification and differentiation of the heart is conserved from flies to mammals [reviewed in (Bodmer and Frasch 1999, Bodmer et al. 2005, Cripps and Olson 2002, Zaffran and Frasch 2002 ], laying the ground work for molecular models of congenital heart disease in humans [reviewed in (Chien and Olson 2002, Prall et al. 2002, Seidman and Seidman 2002, Olson 2004, Srivastava 2006]. Given the remarkable conservation of molecular and embryological mechanisms underlying cardiogenesis in the animal kingdom, it seems plausible that the genetic control of heart function may also be conserved. Clearly, many proteins that carry out cardiac function, such as ion channels and contractile proteins, are highly conserved (reviewed in Bodmer et al. 2005): contributors to excitation-contraction coupling, such as the ryanodine receptor, SERCA, myosin, troponin, and ion channels likely to be involved in pacemaking, such as Ih/HCN (Monier et al. 2005), are all present in fly cardiomyocytes. Also, plasma membrane invag inations forming T tubules have been observed in the fly's heart, much like in vertebrates, and the mononucleate cardiomyocytes that comprise the heart tube are electrically connected by GAP junctions formed by innexin proteins in invertebrates. Thus, it is conceivable that the way these conserved proteins function within the mature heart to ensure a normal heartbeat has also evolved from a common evolutionary design that was in place prior to the invertebratevertebrate split.In the following we review recent advances in elucidating the genetics of cardiac function and aging in Drosophila and propose that the control of the cardiac physiology and rhythmicity is conserved between in many ways vertebrates and invertebrates. As a consequence, the fly heart is a potentially useful genetic model not only for understanding congenital heart disease that Correspondence: R. Bodmer (rolf@burnham.org) and X. Wu

Forkhead Transcription Factors Coordinate Expression of Myocardial KATP Channel Subunits and Energy Metabolism

“…17 Moreover, recent work suggests that FoxO and KATP channels reduce cardiac ageing and electrical instability in drosophila. 59 Our results thus link tissue stress and expression of Fox and KATP channels into a coherent framework.Other sensors of energy status impact on the expression and function of Foxs. AMP kinase (AMPK) 60 -62 may signal metabolic stress (AMP/ATP ratio) to Fox.…”

Drosophila Model of Congenital Heart Diseases

“…The cardiac proteasomes of the mouse and the fly have been shown to be www.intechopen.com comparable with respect to their overall composition (Cammarato et al, 2011), and functional analysis revealed further evidence of the conserved cardiac characteristics of the fly heart (e.g. Ocorr et al, 2007a;Buechling et al, 2009;Choma et al, 2010). In particular, the contractile and electrical properties have been investigated in the Drosophila heart and found to be remarkably similar in fundamental aspects, such as the contribution of ion channels to heart contraction or the effects of mutations of genes of the myofibrillar apparatus (K. Ocorr, unpublished and Lalevée et al, 2006;Wolf et al, 2006;Ocorr et al, 2007b;Cammarato et al, 2008b;Mery et al, 2008).…”

Pathologies et vieillissement cardiaque

“…Une étude pionnière [36] a mis en évidence, que chez la mouche, le vieillissement s'accompagne d'une diminution de la réserve cardiaque 4 et d'une augmentation des arythmies, deux caractéristiques centrales du vieillissement qui sont partagées avec les mammifères. D'autres études [37][38][39] ont depuis largement confirmé ces observations. Elles ont montré que le vieillissement s'accompagne également d'une diminution du débit cardiaque [39,40] et de défauts structuraux au niveau des cardiomyocytes, qui sont liés à une désorga-nisation progressive du réseau de myofibrilles [20].…”