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In JoVE (2)
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Articles by Georg Vogler in JoVE
JoVE General
Флуоресцентная маркировка Drosophila Структур сердца
1Biology Department, San Diego State University, 2Development and Aging Program, NASCR Center, The Sanford Burnham Institute for Medical Research
Здесь мы опишем основные протокол для флуоресцентной маркировки различных элементов сердце труб из личинки и взрослых
JoVE General
Визуализация бьющееся сердце в Drosophila
Development and Aging Program, The Sanford Burnham Institute for Medical Research
Техника, необходимые для визуализации бьющееся сердце в личинок и взрослых
Other articles by Georg Vogler on PubMed
Timing of Identity: Spatiotemporal Regulation of Hunchback in Neuroblast Lineages of Drosophila by Seven-up and Prospero
Neural stem cells often generate different cell types in a fixed birth order as a result of temporal specification of the progenitors. In Drosophila, the first temporal identity of most neural stem cells (neuroblasts) in the embryonic ventral nerve cord is specified by the transient expression of the transcription factor Hunchback. When reaching the next temporal identity, this expression is switched off in the neuroblasts by seven up (svp) in a mitosis-dependent manner, but is maintained in their progeny (ganglion mother cells). We show that svp mRNA is already expressed in the neuroblasts before this division. After mitosis, Svp protein accumulates in both cells, but the downregulation of hunchback (hb) occurs only in the neuroblast. In the ganglion mother cell, svp is repressed by Prospero, a transcription factor asymmetrically localised to this cell during mitosis. Thus, the differential regulation of hb between the neuroblasts and the ganglion mother cells is achieved by a mechanism that integrates information created by the asymmetric distribution of a cell-fate determinant upon mitosis (Prospero) and a transcriptional repressor present in both cells (Seven-up). Strikingly, although the complete downregulation of hb is mitosis dependent, the lineage-specific timing of svp upregulation is not.
The Transcription Factor Zfh1 is Involved in the Regulation of Neuropeptide Expression and Growth of Larval Neuromuscular Junctions in Drosophila Melanogaster
Different aspects of neural development are tightly regulated and the underlying mechanisms have to be transcriptionally well controlled. Here we present evidence that the transcription factor Zfh1, the Drosophila member of the conserved zfh1 gene family, is important for different steps of neuronal differentiation. First, we show that late larval expression of the neuropeptide FMRFamide is dependent on correct levels of Zfh1 and that this regulation is presumably direct via a conserved zfh1 homeodomain binding site in the FMRFamide enhancer. Using MARCM analysis we additionally examined the requirement for Zfh1 during embryonic and larval stages of motoneuron development. We could show that Zfh1 cell autonomously regulates motoneuronal outgrowth and larval growth of neuromuscular junctions (NMJs). In addition, we find that the growth of NMJs is dependent on the dosage of Zfh1, suggesting it to be a downstream effector of the known NMJ size regulating pathways.
Non-autonomous Modulation of Heart Rhythm, Contractility and Morphology in Adult Fruit Flies
The outermost layer of the vertebrate heart originates from migratory mesothelial cells (epicardium) that give rise to coronary vascular smooth muscles and fibroblasts. The role of the epicardium in myocardial morphogenesis and establishment of normal heart function is still largely unknown. Here, we use Drosophila to investigate non-autonomous influences of epicardial-like tissue surrounding the heart tube on the structural and functional integrity of the myocardium. It has previously been shown that during Drosophila heart formation, mesodermal expression of the homeobox transcription factor even-skipped (eve) is required for specification of a subset of non-myocardial progenitors in the precardiac mesoderm. These progenitors may share some similarities with the vertebrate epicardium. To investigate a non-autonomous epicardial-like influence on myocardial physiology, we studied the consequences of reduced mesodermal Eve expression and epi/pericardial cell numbers on the maturation of the myocardial heart tube, its contractility, and acquisition of a normal heart rhythm in the Drosophila model. Targeting the eve repressor ladybird early (lbe) with the minimal eve mesodermal enhancer efficiently eliminates the mesodermal Eve lineages. These flies exhibit defects in heart structure, including a reduction in systolic and diastolic diameter (akin to 'restrictive cardiomyopathy'). They also exhibit an elevated incidence of arrhythmias and intermittent asystoles, as well as compromised performance under stress. These abnormalities are restored by eve reexpression or by lbe-RNAi co-overexpression. The data suggest that adult heart function in Drosophila is likely to be modulated non-autonomously, possibly by paracrine influences from neighboring cells, such as the epi/pericardium. Thus, Drosophila may serve as a model for finding genetic effectors of epicardial-myocardial interactions relevant to higher organisms.
Tinman/Nkx2-5 Acts Via MiR-1 and Upstream of Cdc42 to Regulate Heart Function Across Species
Unraveling the gene regulatory networks that govern development and function of the mammalian heart is critical for the rational design of therapeutic interventions in human heart disease. Using the Drosophila heart as a platform for identifying novel gene interactions leading to heart disease, we found that the Rho-GTPase Cdc42 cooperates with the cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired cardiac output and altered myofibrillar architecture, and adult heart-specific interference with Cdc42 function is sufficient to cause these same defects. We also identified K(+) channels, encoded by dSUR and slowpoke, as potential effectors of the Cdc42-Tinman interaction. To determine whether a Cdc42-Nkx2-5 interaction is conserved in the mammalian heart, we examined compound heterozygous mutant mice and found conduction system and cardiac output defects. In exploring the mechanism of Nkx2-5 interaction with Cdc42, we demonstrated that mouse Cdc42 was a target of, and negatively regulated by miR-1, which itself was negatively regulated by Nkx2-5 in the mouse heart and by Tinman in the fly heart. We conclude that Cdc42 plays a conserved role in regulating heart function and is an indirect target of Tinman/Nkx2-5 via miR-1.
