Transcriptional Regulation of Cardiac Development: Implications for Congenital Heart Disease and DiGeorge Syndrome

Epstein, Jonathan A.; Buck, Clayton A.

doi:10.1203/00006450-200012000-00003

Cited by 51 publications

(38 citation statements)

References 104 publications

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“…Almost simultaneously with the epicardium formation, the cardiac neural crest cells migrate from the dorsal neural tube into the heart to give rise to the vascular smooth muscle of the aortic arch, ductus arteriosus and great vessels (Epstein and Buck, 2000). Understanding the tight spatial and temporal control of differentiation and unravel novel marker genes for these heart cell lineages is critical for a better knowledge of the molecular control of cardiogenesis which in turn has major implications for treating both congenital and adult heart diseases.…”

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confidence: 99%

Ccbe1 expression marks the cardiac and lymphatic progenitor lineages during early stages of mouse development

Facucho-Oliveira¹,

Bento²,

Belo³

2011

Int. J. Dev. Biol.

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The mammalian heart is a complex organ composed of diverse components and various cell types. Heart organogenesis requires the contribution of distinct pools of heart progenitors positioned in separate embryonic regions and subject to particular developmental signals. Moreover, these embryonic heart lineages have different transcriptional profiles expressing specific genes which activate pathways involved in heart lineage specification. Understanding the molecular control of heart organogenesis has major implications for treating congenital and adult heart diseases since specific heart lineages have been associated with particular human cardiovascular malformations. Collagen and calcium-binding EGF-like domain 1 (Ccbe1) was identified in our laboratory using an Affymetrix GeneChip system approach to identify the transcriptome of chick heart/hemangioblast precursor cells. Here, we present a detailed and systematic analysis of the expression of Ccbe1 during early mouse development using whole-mount in situ hybridization (WISH), immunohistochemistry and histological techniques. Ccbe1 mRNA was initially detected in the early cardiac progenitors of the two bilateral cardiogenic fields (E7.0) and in the cardiogenic mesoderm (E7.5 to E8.0). Ccbe1 mRNA was then persistently detected in the pericardium and transiently expressed in the myocardial tissue of the primitive heart tube (E8.25), being later expressed in the proepicardium. By E9.5, the Ccbe1 and Prox1 proteins were found to be expressed in common regions, including the septum transversum and in the proximity of the anterior cardinal vein. Here, it is shown that Ccbe1 is expressed in the FHF, SHF and proepicardium during heart organogenesis (E7.0 to E8.75). Later in development, Ccbe1 expression is localized in the septum transversum and in the vicinity of the anterior cardinal vein, embryonic structures related to hepatic and lymphatic development, respectively. KEY WORDS: Ccbe1, cardiogenic mesoderm, proepicardium, cardiogenesis, lymphangiogenesisCardiogenesis is dependent on three major pools of embryonic heart progenitors that are spatially and temporally segregated in the developing embryo and give rise to distinct cardiac structures (Harvey, 2002;Laugwitz et al., 2008). The cardiogenic mesoderm is the first major source of heart cell precursors to be identified during heart development (embryonic day (E) 7.0) and consists of two different population of heart progenitors, the first heart field (FHF) and the second heart field (SHF). The FHF is derived from the anterior splanchnic mesoderm and gives rise to the primitive heart tube that ultimately generates the bulk of the atrial chambers and the left ventriculum (Laugwitz et al., 2008;Vincent and Buckingham, 2010). The SHF is derived from the pharyngeal mesoderm and contributes to the outflow tract, the right ventricular Int.

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confidence: 99%

Ccbe1 expression marks the cardiac and lymphatic progenitor lineages during early stages of mouse development

Facucho-Oliveira¹,

Bento²,

Belo³

2011

Int. J. Dev. Biol.

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“…During gestation, the PAAs link the heart with paired dorsal aortae and develop symmetrically until approximately E11.5. The PAAs then undergo a dramatic remodeling process that requires the presence of neural crest cells to establish the embryonic asymmetric circulatory system (reviews Creazzo et al, 1998;Sucov, 1998;Epstein and Buck, 2000). The aberrant persistence and/or regression of different components of the PAA system is Fig.…”

Section: Discussionmentioning

confidence: 99%

Effects of genetic background on cardiovascular anomalies in the Ts16 mouse

Villar

Kim

Blank

et al. 2004

Developmental Dynamics

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To investigate the genetic contribution to phenotypic variability in aneuploidy, we generated mice with trisomy 16 (Ts16) by mating [Rb(6.16)24Lub ؋ Rb(16.17)7Bnr]F1 males with females from four inbred strains, BALB/cJ, C3H/HeJ, C57BL/6J, and DBA/2J. Among the four Ts16 strains that were generated, there were no significant differences in survival, weight, or length relative to euploid control littermates at either embryonic day (E) 14.5 or E17.5. All Ts16 fetuses at E14.5 had edema that ranged from mild to severe, increased amniotic fluid volume, and a thickened neck. At E17.5, Ts16 fetuses exhibited two distinct phenotypes, one with an edematous morphology and the other runt-like. None of these gross morphological abnormalities was strain-specific either in occurrence or frequency. At E10.5, there were pharyngeal arch artery (PAA) anomalies in all Ts16 embryos on the C3H/HeJ background, but none in trisomics on the other three backgrounds. However, at E17.5, there was in addition to ventricular and atrioventricular septal defects, a high frequency of aortic arch defects in Ts16 fetuses, irrespective of genetic background. Taken together, these findings indicate that there are at least two mechanistic responses to the presence of three copies of mouse chromosome 16 in the modeling of the cardiovascular system: one, development of PAA defects, is strongly influenced by genetic background; but the second, development of aortic arch anomalies in the absence of preexisting PAA anomalies, is not. INTRODUCTIONAlthough the overall patterns of anomalies and minor variations in development that are characteristic of chromosomal disorders are quite distinct, these conditions are notable for the variability of their phenotypes. For example, in Down syndrome (DS), which results from trisomy 21, none of the typical physical features is present in all affected individuals, and it is very unlikely that two persons would be phenotypically identical. In the case of the major congenital malformations known to be associated with DS, congenital heart disease occurs only half of the time, and duodenal atresia or stenosis in only 2.5% (Epstein, 2001).Several possible explanations for this phenotypic variability in aneuploidy have been suggested (Epstein, 1988). One is that allelic differences in the genes that are triplicated might have different effects when present in three copies. For example, heterotrisomy for a gene (or genes) within a 9.6 cM minimal region (D21S167) on human chromosome 21 has been postulated to be a contributing factor to the pathogenesis of ventricular septal defects (VSDs) in DS, either through the presence of three different specific alleles or through the presence of specific combinations of alleles (Baptista et al., 2000). Second, the overall genetic background of the individual in whom the aneuploidy occurs could affect the penetrance and expression of different phenotypic features. Precedents for such background effects, often attributable to the existence of modifier loci, exist for many genetic trait...

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“…23 Robida et al, [60] Norway 1987-1990 10. 2 Meberg et al, [61] Karachi 1987-1992 4 Hassan et al, [62] Central Australia 1993-2000 17. 5 Bolisetty et al, 63 South Australia 1993-2000 12 Annual report 2000 [64] Oman 1994-1996 7.1 Subramanyan et al, [65] Bosnia 1994-1999 6.12 Begic et al, [66] Egypt 1995-1996 1.01 Bassili et al, [67] Shimla 1995 2.…”

Section: Classification Of Chdsmentioning

confidence: 99%

“…25 Thakur et al, [8] Saudi Arabia 1997-2000 2.4 Alabdulgader [68] New Delhi 2001 4. 2 Chadha et al, [7] In cases where the heart is the only organ, which is transposed, known as isolated Dextro-cardia, there are usually other severe cardiac abnormalities associated with it. Despite a large number of cardiac diseases that exist, there are only a limited number of physiological disturbances that can be produced.…”

Section: Classification Of Chdsmentioning

confidence: 99%

“…Candidate genes that play critical functions at specific stages of cardiac development are emerging from studies in vertebrate and invertebrate model organisms, providing possible cause for various forms of CHDs in human beings. [1][2] The recent discovery that dominant inherited transcription factor mutations cause CHDs has brought direct medical relevance to the study of cardiac transcription factors in heart development. [3] This review focuses on the understandings of the different types of CHDs with some of the associated chromosomal syndromes and the recent developments involving the genetics of CHDs in human beings.…”

Section: Introductionmentioning

confidence: 99%

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