Heart tube patterning in Drosophila requires integration of axial and segmental information provided by the Bithorax Complex genes and hedgehog signaling

Development ◽  
2002 ◽  
Vol 129 (19) ◽  
pp. 4509-4521 ◽  
Author(s):  
Romina Ponzielli ◽  
Martine Astier ◽  
Aymeric Chartier ◽  
Armel Gallet ◽  
Pascal Thérond ◽  
...  

The Drosophila larval cardiac tube is composed of 104 cardiomyocytes that exhibit genetic and functional diversity. The tube is divided into the aorta and the heart proper that encompass the anterior and posterior parts of the tube, respectively. Differentiation into aorta and heart cardiomyocytes takes place during embryogenesis. We have observed living embryos to correlate morphological changes occurring during the late phases of cardiogenesis with the acquisition of organ function, including functional inlets, or ostiae. Cardiac cells diversity originates in response to two types of spatial information such that cells differentiate according to their position, both within a segment and along the anteroposterior axis. Axial patterning is controlled by homeotic genes of the Bithorax Complex (BXC) which are regionally expressed within the cardiac tube in non-overlapping domains. Ultrabithorax (Ubx) is expressed in the aorta whereas abdominal A (abd-A) is expressed in the heart, with the exception of the four most posterior cardiac cells which express Abdominal B (Abd-B). Ubx and abd-A functions are required to confer an aorta or a heart identity on cardiomyocytes, respectively. The anterior limit of the expression domain of Ubx, abd-A and Abd-B is independent of the function of the other genes. In contrast, abd-A represses Ubx expression in the heart and ectopic overexpression of abd-A transforms aorta cells into heart cardiomyocytes. Taken together, these results support the idea that BXC homeotic genes in the cardiac tube conform to the posterior prevalence rule. The cardiac tube is also segmentally patterned and each metamere contains six pairs of cardioblasts that are genetically diverse. We show that the transcription of seven up (svp), which is expressed in the two most posterior pairs of cardioblasts in each segment, is dependent on hedgehog (hh) signaling from the dorsal ectoderm. In combination with the axial information furnished by abd-A, the segmental hh-dependent information leads to the differentiation of the six pairs of svp-expressing cells into functional ostiae. Movies available on-line

Development ◽  
1994 ◽  
Vol 120 (4) ◽  
pp. 871-883 ◽  
Author(s):  
K.E. Yutzey ◽  
J.T. Rhee ◽  
D. Bader

A unique myosin heavy chain cDNA (AMHC1), which is expressed exclusively in the atria of the developing chicken heart, was isolated and used to study the generation of diversified cardiac myocyte cell lineages. The pattern of AMHC1 gene expression during heart formation was determined by whole-mount in situ hybridization. AMHC1 is first activated in the posterior segment of the heart when these myocytes initially differentiate (Hamburger and Hamilton stage 9+). The anterior segment of the heart at this stage does not express AMHC1 although the ventricular myosin heavy chain isoform is strongly expressed beginning at stage 8+. Throughout chicken development, AMHC1 continues to be expressed in the posterior heart tube as it develops into the diversified atria. The early activation of AMHC1 expression in the posterior cardiac myocytes suggests that the heart cells are diversified when they differentiate initially and that the anterior heart progenitors differ from the posterior heart progenitors in their myosin isoform gene expression. The expression domain of AMHC1 can be expanded anteriorly within the heart tube by treating embryos with retinoic acid as the heart primordia fuse. Embryos treated with retinoic acid prior to the initiation of fusion of the heart primordia express AMHC1 throughout the entire heart-forming region and fusion of the heart primordia is inhibited. These data indicate that retinoic acid treatment produces an expansion of the posterior (atrial) domain of the heart and suggests that diversified fates of cardiomyogenic progenitors can be altered.


Development ◽  
1998 ◽  
Vol 125 (13) ◽  
pp. 2489-2498 ◽  
Author(s):  
F. Emily-Fenouil ◽  
C. Ghiglione ◽  
G. Lhomond ◽  
T. Lepage ◽  
C. Gache

In the sea urchin embryo, the animal-vegetal axis is defined before fertilization and different embryonic territories are established along this axis by mechanisms which are largely unknown. Significantly, the boundaries of these territories can be shifted by treatment with various reagents including zinc and lithium. We have isolated and characterized a sea urchin homolog of GSK3beta/shaggy, a lithium-sensitive kinase which is a component of the Wnt pathway and known to be involved in axial patterning in other embryos including Xenopus. The effects of overexpressing the normal and mutant forms of GSK3beta derived either from sea urchin or Xenopus were analyzed by observation of the morphology of 48 hour embryos (pluteus stage) and by monitoring spatial expression of the hatching enzyme (HE) gene, a very early gene whose expression is restricted to an animal domain with a sharp border roughly coinciding with the future ectoderm / endoderm boundary. Inactive forms of GSK3beta predicted to have a dominant-negative activity, vegetalized the embryo and decreased the size of the HE expression domain, apparently by shifting the boundary towards the animal pole. These effects are similar to, but even stronger than, those of lithium. Conversely, overexpression of wild-type GSK3beta animalized the embryo and caused the HE domain to enlarge towards the vegetal pole. Unlike zinc treatment, GSK3beta overexpression thus appeared to provoke a true animalization, through extension of the presumptive ectoderm territory. These results indicate that in sea urchin embryos the level of GSKbeta activity controls the position of the boundary between the presumptive ectoderm and endoderm territories and thus, the relative extent of these tissue layers in late embryos. GSK3beta and probably other downstream components of the Wnt pathway thus mediate patterning both along the primary AV axis of the sea urchin embryo and along the dorsal-ventral axis in Xenopus, suggesting a conserved basis for axial patterning between invertebrate and vertebrate in deuterostomes.


Development ◽  
2021 ◽  
Author(s):  
Cristiana Dondi ◽  
Benjamin Bertin ◽  
Jean-Philippe Daponte ◽  
Inga Wojtowicz ◽  
Krzysztof Jagla ◽  
...  

The formation of the cardiac tube is a remarkable example of complex morphogenetic processes conserved from invertebrates to humans. It involves coordinated collective migration of contralateral rows of cardiac cells. The molecular processes underlying the specification of cardioblasts (CBs) prior to migration are well established and significant advances have been made in understanding the process of lumen formation. However, the mechanisms of collective cardiac cells migration remain elusive. Here we identified CAP and MSP300 as novel actors involved during CBs migration. They both exhibit highly similar temporal and spatial expression patterns in migrating cardiac cells and are necessary for the correct number and alignment of CBs, a prerequisite for the coordination of their collective migration. Our data suggest that CAP and MSP300 are part of a protein complex linking focal adhesion sites to nuclei via the actin cytoskeleton that maintains post-mitotic state and correct alignment of CBs.


1988 ◽  
Vol 107 (6) ◽  
pp. 2575-2586 ◽  
Author(s):  
D L Ruzicka ◽  
R J Schwartz

The expression of cytoplasmic beta-actin and cardiac, skeletal, and smooth muscle alpha-actins during early avian cardiogenesis was analyzed by in situ hybridization with mRNA-specific single-stranded DNA probes. The cytoplasmic beta-actin gene was ubiquitously expressed in the early chicken embryo. In contrast, the alpha-actin genes were sequentially activated in avian cardiac tissue during the early stages of heart tube formation. The accumulation of large quantities of smooth muscle alpha-actin transcripts in epimyocardial cells preceded the expression of the sarcomeric alpha-actin genes. The accumulation of skeletal alpha-actin mRNAs in the developing heart lagged behind that of cardiac alpha-actin by several embryonic stages. At Hamburger-Hamilton stage 12, the smooth muscle alpha-actin gene was selectively down-regulated in the heart such that only the conus, which subsequently participates in the formation of the vascular trunks, continued to express this gene. This modulation in smooth muscle alpha-actin gene expression correlated with the beginning of coexpression of sarcomeric alpha-actin transcripts in the epimyocardium and the onset of circulation in the embryo. The specific expression of the vascular smooth muscle alpha-actin gene marks the onset of differentiation of cardiac cells and represents the first demonstration of coexpression of both smooth muscle and striated alpha-actin genes within myogenic cells.


Development ◽  
1995 ◽  
Vol 121 (6) ◽  
pp. 1681-1689 ◽  
Author(s):  
A. Chiang ◽  
M.B. O'Connor ◽  
R. Paro ◽  
J. Simon ◽  
W. Bender

The Polycomb protein of Drosophila melanogaster maintains the segmental expression limits of the homeotic genes in the bithorax complex. Polycomb-binding sites within the bithorax complex were mapped by immunostaining of salivary gland polytene chromosomes. Polycomb bound to four DNA fragments, one in each of four successive parasegmental regulatory regions. These fragments correspond exactly to the ones that can maintain segmentally limited expression of a lacZ reporter gene. Thus, Polycomb acts directly on discrete multiple sites in bithorax regulatory DNA. Constructs combining fragments from different regulatory regions demonstrate that Polycomb-dependent maintenance elements can act on multiple pattern initiation elements, and that maintenance elements can work together. The cooperative action of maintenance elements may motivate the linear order of the bithorax complex.


2017 ◽  
Vol 51 (2) ◽  
pp. 132-151 ◽  
Author(s):  
Albina Kinga Moscicka

Purpose The purpose of this paper is to propose a way of using already existing archival resources in the geographic information system (GIS). Design/methodology/approach The essence of the methodology used was to identify semantic relations of archival documents with geographical space and develop their metadata into spatially related metadata, ready to use in GIS and to join geographical names occurring in these metadata with exact places to which they were related to. Research was based on two digital collections from the Library of Contemporary History in Stuttgart on-line service. These collections were related to the First World War and they included metadata prepared in MAB standard. Findings As the results of the research, two sample metadata sets related to posters and ration coupons were developed. Thesauruses of coordinates of places and regions mentioned in documents metadata in different semantic context were also created. To complete the methodology, the assumptions of the GIS structure and concept of applying metadata in them, have been proposed. Research limitations/implications The research also presents limitations in effective implementation of the proposed solutions, which lie mainly in lack of rules and consequences in recording geographical names in metadata. Originality/value The value of the proposed solution is easy way of using already existing data in GIS and possibilities of gathering, managing, presenting and analyzing archives with one parameter more than in traditional databases – with spatial information. The added value and an effective use of already collected data lies in the strong recommendation of defining and implementation of rules for recording geographical names in archival documents metadata. This will help in a wide use of collected data in any spatial-based solutions as well as in automation of process of joining archives with geographical space, and finally in dissemination of collected resources.


2019 ◽  
Vol 30 (4) ◽  
pp. 526-540 ◽  
Author(s):  
Nicole Hakim ◽  
Kirsten C. S. Adam ◽  
Eren Gunseli ◽  
Edward Awh ◽  
Edward K. Vogel

Complex cognition relies on both on-line representations in working memory (WM), said to reside in the focus of attention, and passive off-line representations of related information. Here, we dissected the focus of attention by showing that distinct neural signals index the on-line storage of objects and sustained spatial attention. We recorded electroencephalogram (EEG) activity during two tasks that employed identical stimulus displays but varied the relative demands for object storage and spatial attention. We found distinct delay-period signatures for an attention task (which required only spatial attention) and a WM task (which invoked both spatial attention and object storage). Although both tasks required active maintenance of spatial information, only the WM task elicited robust contralateral delay activity that was sensitive to mnemonic load. Thus, we argue that the focus of attention is maintained via a collaboration between distinct processes for covert spatial orienting and object-based storage.


2011 ◽  
Vol 301 (4) ◽  
pp. H1531-H1539 ◽  
Author(s):  
Hidekazu Ishida ◽  
Shigetoyo Kogaki ◽  
Jun Narita ◽  
Hiroaki Ichimori ◽  
Nobutoshi Nawa ◽  
...  

LEOPARD syndrome (LS) is an autosomal dominant inherited multisystemic disorder. Most cases involve mutations in the PTPN11 gene, which encodes the protein tyrosine phosphatase Src homology 2-containing protein phosphatase 2 (SHP2). LS frequently causes severe hypertrophic cardiomyopathy (HCM), even from the fetal period. However, the molecular pathogenesis has not been clearly elucidated. Here, we analyzed the roles of the LS-type SHP2 mutant Gln510Glu (Q510E), which showed the most severe type of HCM in LS, in cardiomyocyte differentiation, and in morphological changes. We generated mutant P19CL6 cell lines, the most convenient cardiomyocyte differentiation model, which continuously expressed SHP2-Q510E, SHP2-D61N (Noonan-type mutant), wild-type SHP2, and green fluorescent protein (native SHP2 expression only). SHP2-Q510E mutant P19CL6 cells showed significant attenuation of myofibrillogenesis, with increased proliferative activity. Mature cardiomyocytes from the SHP2-Q510E mutant were significantly larger than those of controls and the other mutants. However, expression of cardiac-specific transcriptional factors (Gata4, Tbx5, and Nkx2.5) did not differ significantly between the LS-type SHP2-Q510E mutants and the other mutants and controls. Our results indicate that SHP2-Q510E mutants can differentiate into cardiac progenitors but are inhibited from undergoing terminal differentiation into mature cardiomyocytes. In contrast, Akt and glycogen synthase kinase (GSK)-3β phosphorylation were upregulated, and nuclear β-catenin at the late stage of differentiation was highly accumulated in SHP2-Q510E mutant P19CL6 cells. Supplementation with the phosphoinositide 3-kinase/Akt inhibitor LY-294002 during the late stage of differentiation was found to partially restore myofibrillogenesis while suppressing the increase in size of individual mature cardiomyocytes derived from the SHP2-Q510E mutants. Our findings suggest that dysregulation of the Akt/GSK-3β/β-catenin pathway can contribute to the pathogenesis of HCM in LS patients, not only through hypertrophic changes in individual cardiac cells but also via the expansion of cardiac progenitors.


1999 ◽  
Vol 31 (1) ◽  
pp. 39-53 ◽  
Author(s):  
Martin J. Farrell ◽  
James A. Thomson
Keyword(s):  

2002 ◽  
Vol 22 (22) ◽  
pp. 8026-8034 ◽  
Author(s):  
Gerhard Rank ◽  
Matthias Prestel ◽  
Renato Paro

ABSTRACT The proteins of the trithorax and Polycomb groups maintain the differential expression pattern of homeotic genes established by the early embryonic patterning system during development. These proteins generate stable and heritable chromatin structures by acting via particular chromosomal memory elements. We established a transgenic assay system showing that the Polycomb group response elements bxd and Mcp confer epigenetic inheritance throughout development. With previously published data for the Fab7 cellular memory module, we confirmed the cellular memory function of Polycomb group response elements. In Drosophila melanogaster, several of these memory elements are located in the large intergenic regulatory regions of the homeotic bithorax complex. Using a transgene assay, we showed that transcription through a memory element correlated with the relief of silencing imposed by the Polycomb group proteins and established an epigenetically heritable active chromatin mode. A memory element remodeled by the process of transcription was able to maintain active expression of a reporter gene throughout development. Thus, transcription appears to reset and change epigenetic marks at chromosomal memory elements regulated by the Polycomb and trithorax proteins. Interestingly, in the bithorax complex of D. melanogaster, the segment-specific expression of noncoding intergenic transcripts during embryogenesis seems to fulfill this switching role for memory elements regulating the homeotic genes.


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