Homocysteine enhances cardiac neural crest cell attachment in vitro by increasing intracellular calcium levels

Heidenreich, David; Reedy, Mark V.; Brauer, Philip R.

doi:10.1002/dvdy.21644

Cited by 8 publications

(9 citation statements)

References 83 publications

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“…The CHD that result from exposure to elevated homocysteine, especially those effecting the outflow tract, are likely to be related to the impact that homocysteine has upon the development of the cardiac neural crest, (Brauer and Rosenquist, 2002;Boot et al, 2003Boot et al, , 2004Boot et al, , 2006Tierney et al, 2004;Rosenquist et al, 2007;Heidenreich et al, 2008). A number of biological, chemical, and genetic mechanisms have been postulated for the teratogenic effect of homocysteine during heart development, some of which have been reviewed previously van Mil et al, 2010).…”

Section: Indirect Effects Of Insufficent Folate Upon the Cardiac Neurmentioning

confidence: 99%

Folate, Homocysteine and the Cardiac Neural Crest

Rosenquist

2013

Developmental Dynamics

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Congenital heart defects (CHD) are the most common congenital defects worldwide, and perigestational folate supplementation (PFS) is the most effective large-scale intervention to date for reducing CHD. This review is based upon the following premises: that the majority of CHD result from disruption of development of the cardiac neural crest (CNC); and that the CNC is highly responsive to folate and homocysteine. The following roles of folate are discussed in relation to CNC development: one-carbon metabolism in support of mitosis and gene methylation; and gene regulation via direct activity of the folate receptor. The following roles of hyperhomocysteinemia are discussed in the same context: increased oxidative stress; disruption of gene methylation; homocysteinylation of key proteins; and NMDA receptor binding. It is proposed that well-focused advances in folate-CNC research could lead to development of strategies, in addition to PFS, to facilitate normal CNC and heart development, and thereby further reduce CHD.

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Section: Indirect Effects Of Insufficent Folate Upon the Cardiac Neurmentioning

confidence: 99%

Folate, Homocysteine and the Cardiac Neural Crest

Rosenquist

2013

Developmental Dynamics

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“…Alternatively, it has been hypothesized that the increase in homocysteine that accompanies folate insufficiency is the actual risk factor. We [12-14] and others [15,16] have shown that hyperhomocysteinemia is associated with conotruncal defects in the chicken embryo model, while recent evidence indicates that maternal hyperhomocysteinemia also may be associated with conotruncal defects in humans [17]. In fact it appears that hyperhomocysteinemia, rather than hypomethylation, is a more important risk factor in the development of heart defects [18].…”

Section: Introductionmentioning

confidence: 99%

The N-methyl-d-aspartate receptor in heart development: A gene knockdown model using siRNA

Lie¹,

Bennett²,

Rosenquist³

2010

Reproductive Toxicology

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Antagonists of the N-methyl-D-aspartate receptor (NMDAR) may disrupt the development of the cardiac neural crest (CNC) and contribute to conotruncal heart defects. To test this interaction, a lossof-function model was generated using small interfering RNAs (siRNA) directed against the critical NR1-subunit of this receptor in avian embryos. The coding sequence of the chicken NR1-gene and predicted protein sequences were characterized and found to be homologous with other vertebrate species. Analysis of its spatiotemporal expression demonstrated its expression within the neural tube at pre-migratory CNC sites. siRNA targeted to the NR1-mRNA in pre-migratory CNC lead to a significant decrease in NR1 protein expression. However, embryo survival and heart development were not adversely affected. These results indicate that the CNC may function normally in the absence of functional NMDAR, and that NMDAR antagonists may have a complex impact upon the CNC that transcends impairment of a single receptor type.

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“…We have previously shown that early emerging trunk NC cells reach the DA in discrete migratory streams through the rostral somite halves, under the guidance of CXCR4/CXCL12 signaling (Kasemeier-Kulesa et al, 2010). We were surprised to find only random calcium transients during NC cell migration in the head and trunk, since previous in vitro studies have identified calcium activities in fibroblasts (Wei et al, 2010), NC cell delamination (Newgreen and Gooday, 1985) and attachment to the substrate (Heidenreich et al, 2008), and motor axon guidance (Hanson and Landmesser, 2004). In contrast, the pattern of calcium transients after NC cells reached the DA was exciting (Figs.…”

Section: Discussionmentioning

confidence: 96%

“…Typical calcium indicators, such as Fluo-4 AM (Heidenreich et al, 2008) require invasive delivery into embryos or can be soaked into cells and tissue in vitro by external application. This severely limits the ability to accurately deliver calcium indicators to discrete cell subpopulations within the developing embryo during precise times of complex morphogenetic events.…”

Section: Introductionmentioning

confidence: 99%

In vivo calcium dynamics during neural crest cell migration and patterning using GCaMP3

McKinney

Kulesa

2011

Developmental Biology

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Examining calcium dynamics within the neural crest (NC) has the potential to shed light on mechanisms that regulate complex cell migration and patterning events during embryogenesis. Unfortunately, typical calcium indicators are added to culture media or have low signal to noise after microinjection into tissue that severely limits analyses to cultured cells or superficial events. Here, we studied in vivo calcium dynamics during NC cell migration and patterning, using a genetically encoded calcium sensor, GCaMP3. We discovered that trunk NC cells displayed significantly more spontaneous calcium transients than cranial NC cells, and during cell aggregation versus cell migration events. Spontaneous calcium transients were more prevalent during NC cell aggregation into discrete sympathetic ganglia (SG). Blocking of N-cadherin activity in trunk NC cells near the presumptive SG led to a dramatic decrease in the frequency of spontaneous calcium transients. Detailed analysis and mathematical modeling of cell behaviors during SG formation showed NC cells aggregated into clusters after displaying a spontaneous calcium transient. This approach highlights the novel application of a genetically encoded calcium indicator to study subsets of cells during ventral events in embryogenesis.

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Homocysteine enhances cardiac neural crest cell attachment in vitro by increasing intracellular calcium levels

Cited by 8 publications

References 83 publications

Folate, Homocysteine and the Cardiac Neural Crest

Folate, Homocysteine and the Cardiac Neural Crest

The N-methyl-d-aspartate receptor in heart development: A gene knockdown model using siRNA

In vivo calcium dynamics during neural crest cell migration and patterning using GCaMP3

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