Steroid-dependent modification of Hox function drives myocyte reprogramming in the Drosophila heart.
Reads0
Chats0
TLDR
In vivo time-lapse analysis shows that the adult fruit fly cardiac tube is formed during metamorphosis by the reprogramming of differentiated and already functional larval cardiomyocytes, without cell proliferation, shedding light on the genetic control of one in vivo occurring remodelling process, which involves a steroid-dependent modification of Hox expression and function.Abstract:
In the Drosophila larval cardiac tube, aorta and heart differentiation are controlled by the Hox genes Ultrabithorax (Ubx) and abdominal A (abdA), respectively. There is evidence that the cardiac tube undergoes extensive morphological and functional changes during metamorphosis to form the adult organ, but both the origin of adult cardiac tube myocytes and the underlying genetic control have not been established. Using in vivo time-lapse analysis, we show that the adult fruit fly cardiac tube is formed during metamorphosis by the reprogramming of differentiated and already functional larval cardiomyocytes, without cell proliferation. We characterise the genetic control of the process, which is cell autonomously ensured by the modulation of Ubx expression and AbdA activity. Larval aorta myocytes are remodelled to differentiate into the functional adult heart, in a process that requires the regulation of Ubx expression. Conversely, the shape, polarity, function and molecular characteristics of the surviving larval contractile heart myocytes are profoundly transformed as these cells are reprogrammed to form the adult terminal chamber. This process is mediated by the regulation of AbdA protein function, which is successively required within these persisting myocytes for the acquisition of both larval and adult differentiated states. Importantly, AbdA specificity is switched at metamorphosis to induce a novel genetic program that leads to differentiation of the terminal chamber. Finally, the steroid hormone ecdysone controls cardiac tube remodelling by impinging on both the regulation of Ubx expression and the modification of AbdA function. Our results shed light on the genetic control of one in vivo occurring remodelling process, which involves a steroid-dependent modification of Hox expression and function.read more
Citations
More filters
Journal ArticleDOI
KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging.
Karen Ocorr,Nick L. Reeves,Nick L. Reeves,Robert Wessells,Robert Wessells,Martin Fink,Martin Fink,H.-S. Vincent Chen,H.-S. Vincent Chen,Takeshi Akasaka,Soichiro Yasuda,Joseph M. Metzger,Wayne R. Giles,Wayne R. Giles,James W. Posakony,Rolf Bodmer +15 more
TL;DR: It is suggested that K+ currents, mediated by a KCNQ channel, contribute to the repolarization reserve of fly hearts, ensuring normal excitation-contraction coupling and rhythmical contraction.
Journal ArticleDOI
Functional variant in microRNA-196a2 contributes to the susceptibility of congenital heart disease in a Chinese population.
Jing Xu,Zhibin Hu,Zhengfeng Xu,Haiyong Gu,Long Yi,Hailong Cao,Jiaping Chen,Tian Tian,Jie Liang,Ying Lin,Wanshan Qiu,Hongxia Ma,Hongbing Shen,Yijiang Chen +13 more
TL;DR: This is the first study to indicate that miR‐196a2 rs11614913 plays a role in sporadic CHD susceptibility, and in vitro binding assays revealed that the rs116 14913 variant affects HOXB8 binding to mature miR •196a.
Journal ArticleDOI
Genetic control of heart function and aging in Drosophila.
TL;DR: The potential for discovery of new genes, such as the two-pore ORK1 K+ channel that affects heart rate in flies, makes Drosophila an attractive heart model for genome-wide screens and for complex genetic manipulations needed to elucidate the mechanisms contributing to cardiac malfunction.
Journal ArticleDOI
Heart development in Drosophila.
Ye Tao,Robert A. Schulz +1 more
TL;DR: Findings on Drosophila heart development are summarized in terms of the regulators and genetic pathways required for cardiac cell specification and differentiation, and organ formation and function.
Journal ArticleDOI
Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype.
Ouarda Taghli-Lamallem,Takeshi Akasaka,Grant Hogg,Uri Nudel,David Yaffe,Jeffrey S. Chamberlain,Karen Ocorr,Rolf Bodmer +7 more
TL;DR: It is shown that the loss of dys function in the heart leads to an age‐dependent disruption of the myofibrillar organization within the myocardium as well as to alterations in cardiac performance, which illustrates the utility of Drosophila as a model system to study dilated cardiomyopathy and other muscular‐dystrophy‐associated phenotypes.
References
More filters
Journal ArticleDOI
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Andrea H. Brand,Norbert Perrimon +1 more
TL;DR: The GAL4 system, a system for targeted gene expression that allows the selective activation of any cloned gene in a wide variety of tissue- and cell-specific patterns, has been designed and used to expand the domain of embryonic expression of the homeobox protein even-skipped.
Journal ArticleDOI
Genetic Transformation of Drosophila with Transposable Element Vectors
TL;DR: A rosy transposon (ry1), constructed by inserting a chromosomal DNA fragment containing the wild-type rosy gene into a P transposable element, transformed germ line cells in 20 to 50 percent of the injected rosy mutant embryos indicating that the visible genetic defect in the host strain could be fully and permanently corrected by the transferred gene.
Book
The Genetics and biology of Drosophila
TL;DR: This is the first attempt since 1925 to publish a comprehensive account of the biology and genetics of Drosophila and it aims to collate the dauntingly large literature on the subject and to make more accessible the private language ot the Dosophilist.
Journal ArticleDOI
Spatiotemporal rescue of memory dysfunction in Drosophila
TL;DR: A method for temporal and regional gene expression targeting in Drosophila is developed and shown the simultaneous spatial and temporal rescue of a memory defect, which rules out a developmental brain defect in the etiology of this deficit.
Journal ArticleDOI
Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid
Michael Kessel,Peter Gruss +1 more
TL;DR: It is suggested that the identity of a vertebral segment is specified by a combination of functionally active Hox genes, a "Hox code," and that exogenous RA interferes with the normal establishment of Hox codes and thus with axial specification.
Related Papers (5)
Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
Andrea H. Brand,Norbert Perrimon +1 more