Hand, an evolutionarily conserved bHLH transcription factor required for<i>Drosophila</i>cardiogenesis and hematopoiesis

Han, Zhe; Yi, Peng; Li, Xiumin; Olson, Eric N.

doi:10.1242/dev.02285

Cited by 110 publications

(98 citation statements)

References 47 publications

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“…Thus, it is not surprising that the cell line QCE-6 above mentioned, which is able to differentiate in endocardium and myocardium, can also give rise to erythrocytes in culture (Eisenberg and Markwald, 1997). It might also be significant that a same transcriptional activator, Hand, be required for both, cardiogenesis and hemopoiesis in Drosophila (Han et al, 2006) under control of the GATA factors pannier and serpent, respectively.…”

Section: The Origin Of the Endocardiummentioning

confidence: 99%

Building the vertebrate heart - an evolutionary approach to cardiac development

2009

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The vertebrate heart is unique among the blood pumps described in metazoans. In contrast to the myoepithelial tubes found in most animal phyla, the vertebrate heart is made up of multilayered myocardial cells surrounded by connective tissue derived from epicardium and endocardium, and endowed with complex valvular, coronary vessel and conduction systems. Despite these profound differences, a common genetic program seems to underlie the specification and differentiation of all the cardiac tissues. In this article, we will review the similarities in the transcriptional networks and signalling mechanisms regulating cardiac development in different animals, as well as the origin of the main differences existing between vertebrate and invertebrate hearts. We will pay special attention to the hypotheses concerning the evolutionary origin of the endothelium and the epicardium from ancestral blood cells and pronephric progenitors, respectively. We can summarize the transition between the invertebrate and the vertebrate heart as the result of the thickening of the primarily myoepithelial cardiac tube which was concomitant with: 1) an inner lining by an endothelium with the ability to transform into mesenchyme; 2) an outer lining derived from an ancestral pronephric glomerular primordium with vasculogenic potential; 3) a neural crest cell population which reaches the heart from the pharyngeal region; 4) the incorporation of new myocardium at both ends from a second heart field and 5) the formation of specialized chambers. The complex interactions between all these elements originated an exceptionally powerful blood pump which allowed vertebrates to reach their characteristically large size and activity.

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Section: The Origin Of the Endocardiummentioning

confidence: 99%

Building the vertebrate heart - an evolutionary approach to cardiac development

2009

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“…Like vertebrates, Drosophila Dmef2 isoforms activate muscle-specific genes and also seems to interact with a conserved cohort of interacting proteins for muscle specification, including cardiogenesis. These include tinman (Azpiazu and Frasch, 1993), dHAND (Han et al, 2006), and the gene encoding the GATA factor Pannier (Pnr; Gajewski et al, 1997). Dissection of the regulatory region of the muscle-specific structural genes, TroponinT (Butler and Ordahl, 1999), TroponinI (TnI), and Tropomyosin (TmI) indicates that cofactors work together with Dmef2 during cardiogenesis in Drosophila (Lin et al, 1996;Mas et al, 2004;Nongthomba et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Alternative Requirements for Vestigial, Scalloped, and Dmef2 during Muscle Differentiation inDrosophila melanogaster

Deng

Hughes

Bell³

et al. 2009

MBoC

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Vertebrate development requires the activity of the myocyte enhancer factor 2 (mef2) gene family for muscle cell specification and subsequent differentiation. Additionally, several muscle-specific functions of MEF2 family proteins require binding additional cofactors including members of the Transcription Enhancing Factor-1 (TEF-1) and Vestigiallike protein families. In Drosophila there is a single mef2 (Dmef2) gene as well single homologues of TEF-1 and vestigial-like, scalloped (sd), and vestigial (vg), respectively. To clarify the role(s) of these factors, we examined the requirements for Vg and Sd during Drosophila muscle specification. We found that both are required for muscle differentiation as loss of sd or vg leads to a reproducible loss of a subset of either cardiac or somatic muscle cells in developing embryos. This muscle requirement for Sd or Vg is cell specific, as ubiquitous overexpression of either or both of these proteins in muscle cells has a deleterious effect on muscle differentiation. Finally, using both in vitro and in vivo binding assays, we determined that Sd, Vg, and Dmef2 can interact directly. Thus, the muscle-specific phenotypes we have associated with Vg or Sd may be a consequence of alternative binding of Vg and/or Sd to Dmef2 forming alternative protein complexes that modify Dmef2 activity. INTRODUCTIONSpecification and differentiation of both vertebrate and invertebrate muscles requires a conserved cohort of transcription factors (Baylies et al., 1998;Cripps and Olson, 2002). Among these, myocyte enhancer factor-2 (MEF2) plays a key role in specification and subsequent differentiation of all muscle types (skeletal, smooth, and heart muscle; Lilly et al., 1995;. There are four different known vertebrate mef2 genes: mef2-a, -b, -c, and -d (Black and Olson, 1998). These four genes produce several different MEF2 isoforms involved in differentiation of all muscle types. In addition, it has been proposed that MEF2 proteins have a requirement for tissue-specific cofactors to confer additional specificity. For example, during mammalian heart development, GATA-4 (Charron and Nemer, 1999) helps to recruit MEF2 to the promoters of cardiac-specific genes including atrial natriuretic factor (ANF) and ␣-cardiac actin (␣-CA; Morin et al., 2000). MEF2 also interacts with another transcription factor, HAND1, during activation of ANF in cardiac cells (Morin et al., 2005). This complex interplay between MEF2 proteins and cofactors is not restricted to cardiac muscles as during skeletal muscle development; MEF2 interacts with MyoD during activation of specific structural genes (Molkentin et al., 1995;.In terms of MEF2 protein family activity, muscle differentiation in Drosophila is relatively less complex as there is only a single homologue mef2, Dmef2 (Lilly et al., 1994). Like vertebrates, Drosophila Dmef2 isoforms activate muscle-specific genes and also seems to interact with a conserved cohort of interacting proteins for muscle specification, including cardiogenesis. These include tinman (Azp...

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“…When 10-kD fluorescentlabeled Dextran was injected into Drosophila larvae, this small-size dye was accumulated by pericardial nephrocyte very efficiently within a few hours ( Figure 1E). Hand-GFP transgene, which is strongly expressed in cardioblasts and pericardial nephrocytes, [17][18][19] was used to label pericardial nephrocytes ( Figure 1E9). The efficiency of dye uptake decreased with larger size; 24 hours after injection, only a low level of 70-kD Dextran accumulation was observed in the pericardial nephrocytes ( Figure 1F), and extra-large 155-kD Dextran was not found in pericardial nephrocytes ( Figure 1G).…”

mentioning

confidence: 99%

An In Vivo Functional Analysis System for Renal Gene Discovery in Drosophila Pericardial Nephrocytes

Zhang¹,

Zhao²,

Han

2013

Journal of the American Society of Nephrology

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101

135

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The difficulty in accessing mammalian nephrons in vivo hinders the study of podocyte biology. The Drosophila nephrocyte shares remarkable similarities to the glomerular podocyte, but the lack of a functional readout for nephrocytes makes it challenging to study this model of the podocyte, which could potentially harness the power of Drosophila genetics. Here, we present a functional analysis of nephrocytes and establish an in vivo system to screen for renal genes. We found that nephrocytes efficiently take up secreted fluorescent protein, and therefore, we generated a transgenic line carrying secreted fluorescent protein and combined it with a nephrocyte-specific driver for targeted gene knockdown, allowing the identification of genes required for nephrocyte function. To validate this system, we examined the effects of knocking down sns and duf, the Drosophila homologs of nephrin and Neph1, respectively, in pericardial nephrocytes. Knockdown of sns or duf completely abolished the accumulation of the fluorescent protein in pericardial nephrocytes. Examining the ultrastructure revealed that the formation of the nephrocyte diaphragm and lacunar structure, which is essential for protein uptake, requires sns. Our preliminary genetic screen also identified Mec2, which encodes the homolog of mammalian Podocin. Taken together, these data suggest that the Drosophila pericardial nephrocyte is a useful in vivo model to help identify genes involved in podocyte biology and facilitate the discovery of renal disease genes.

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Hand, an evolutionarily conserved bHLH transcription factor required forDrosophilacardiogenesis and hematopoiesis

Cited by 110 publications

References 47 publications

Building the vertebrate heart - an evolutionary approach to cardiac development

Building the vertebrate heart - an evolutionary approach to cardiac development

Alternative Requirements for Vestigial, Scalloped, and Dmef2 during Muscle Differentiation inDrosophila melanogaster

An In Vivo Functional Analysis System for Renal Gene Discovery in Drosophila Pericardial Nephrocytes

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