Sustained vs. oscillating expressions of Ngn2, Dll1 and Hes1: A model of neural differentiation of embryonic telencephalon

Barton, Alejandro; Fendrik, A. J.

doi:10.1016/j.jtbi.2013.03.004

Cited by 24 publications

(21 citation statements)

References 26 publications

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“…Further, gestational alcohol exposure alters cortical vascularization in the neonatal brain resulting in reduced expression of VEGF receptors (Jégou et al, 2012). Vascularization, neural development, cell growth, and proliferation are dependent on the oscillatory signaling of Notch pathway components; as such, reduced expression of Hes1 after PAE may alter proliferation of the NPC culture (Barton & Fendrik, 2013; Fischer et al, 2004; Shimojo, Ohtsuka, & Kageyama, 2011). Other studies have demonstrated the sensitivity of Notch signaling to alcohol using several different exposure methods: these include application of 100 mM alcohol on human neural stem cells in vitro (Hashimoto-Torii et al, 2011; Melendez, McGinty, Kalivas, & Becker, 2012) and chronic intermittent (Melendez et al, 2012) or acute in vivo exposure to high doses of alcohol (Rubert, Miñana, Pascual, & Guerri, 2006).…”

Section: Discussionmentioning

confidence: 99%

Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

Tyler

Allan

2014

Alcohol

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Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute high doses in vivo. In this study, we used our established moderate prenatal alcohol exposure (PAE) model, resulting in maternal blood alcohol content of approximately 20 mM, and subsequent ex vivo cell culture to assess expression of genes related to neurogenesis. Proliferating and differentiating neural progenitor cell culture conditions were established from telencephalic tissue derived from embryonic day (E) 15–17 tissue exposed to alcohol via maternal drinking throughout pregnancy. Gene expression analysis on mRNA derived in vitro was performed using a microarray, and quantitative PCR was conducted for genes to validate the microarray. Student's t tests were performed for statistical comparison of each exposure under each culture condition using a 95% confidence interval. Eleven percent of genes on the array had significantly altered mRNA expression in the prenatal alcohol-exposed neural progenitor culture under proliferating conditions. These include reduced expression of Adora2a, Cxcl1, Dlg4, Hes1, Nptx1, and Vegfa and increased expression of Fgf13, Ndn, and Sox3; bioinformatics analysis indicated that these genes are involved in cell growth and proliferation. Decreased levels of Dnmt1 and Dnmt3a were also found under proliferating conditions. Under differentiating conditions, 7.3% of genes had decreased mRNA expression; these include Cdk5rap3, Gdnf, Hey2, Heyl, Pard6b, and Ptn, which are associated with survival and differentiation as indicated by bioinformatics analysis. This study is the first to use chronic low to moderate PAE, to more accurately reflect maternal alcohol consumption, and subsequent neural progenitor cell culture to demonstrate that PAE throughout gestation alters expression of genes involved in neural development and embryonic neurogenesis.

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Section: Discussionmentioning

confidence: 99%

Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

Tyler

Allan

2014

Alcohol

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“…These reciprocal phenotypes suggest that CHD8 and beta-catenin form a regulatory network that controls head size by altering neuronal migration and growth during development (Figure 4). Other proteins with de novo mutations in this network include TBL1XR1, which binds beta-catenin [74], and DLL1, which is expressed in neural progenitor cells and part of the Delta/Notch signaling pathway [75]. …”

Section: Protein Interaction Network Converge On Common Pathwaysmentioning

confidence: 99%

A de novo convergence of autism genetics and molecular neuroscience

Krumm

O’Roak

Shendure

et al. 2014

Trends in Neurosciences

403

356

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Autism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental disorders with large genetic components, but identification of pathogenic genes has proceeded slowly because hundreds of loci are involved. New exome sequencing technology has identified novel rare variants and has found that sporadic cases of ASD/ID are enriched for disruptive de novo mutations. Targeted large-scale resequencing studies have confirmed the significance of specific loci, including chromodomain helicase DNA binding protein 8 (CHD8), sodium channel, voltage-gated, type II, alpha subunit (SCN2A), dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), and catenin (cadherin-associated protein), beta 1, 88 kDa (CTNNB1, beta-catenin). We review recent studies and suggest that they have led to a convergence on three functional pathways: (i) chromatin remodeling; (ii) wnt signaling during development; and (iii) synaptic function. These pathways and genes significantly expand the neurobiological targets for study, and suggest a path for future genetic and functional studies.

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“…Oscillatory expression of Hes1 contributes to the neural differentiation together with the Ngn2, Dll1 oscillation (Barton and Fendrik, 2013), while loss of it leads to retardation of the G (1) phase of the cell cycle (Yoshiura et al, 2007). Furthermore, different levels of HES1 might contribute to heterogeneous responses of ES cells (Kobayashi et al, 2009).…”

Section: Oscilliation Of Hes1 Expressionmentioning

confidence: 99%

Control of hair cell development by molecular pathways involving Atoh1, Hes1 and Hes5

Hou

Yang

2015

Gene

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Sustained vs. oscillating expressions of Ngn2, Dll1 and Hes1: A model of neural differentiation of embryonic telencephalon

Cited by 24 publications

References 26 publications

Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

A de novo convergence of autism genetics and molecular neuroscience

Control of hair cell development by molecular pathways involving Atoh1, Hes1 and Hes5

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