Prenatal alcohol exposure and cellular differentiation: a role for Polycomb and Trithorax group proteins in FAS phenotypes?

Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Alcohol research : current reviews 12/2013; 35(1):77-85.
Source: PubMed


Exposure to alcohol significantly alters the developmental trajectory of progenitor cells and fundamentally compromises tissue formation (i.e., histogenesis). Emerging research suggests that ethanol can impair mammalian development by interfering with the execution of molecular programs governing differentiation. For example, ethanol exposure disrupts cellular migration, changes cell-cell interactions, and alters growth factor signaling pathways. Additionally, ethanol can alter epigenetic mechanisms controlling gene expression. Normally, lineage-specific regulatory factors (i.e., transcription factors) establish the transcriptional networks of each new cell type; the cell's identity then is maintained through epigenetic alterations in the way in which the DNA encoding each gene becomes packaged within the chromatin. Ethanol exposure can induce epigenetic changes that do not induce genetic mutations but nonetheless alter the course of fetal development and result in a large array of patterning defects. Two crucial enzyme complexes--the Polycomb and Trithorax proteins--are central to the epigenetic programs controlling the intricate balance between self-renewal and the execution of cellular differentiation, with diametrically opposed functions. Prenatal ethanol exposure may disrupt the functions of these two enzyme complexes, altering a crucial aspect of mammalian differentiation. Characterizing the involvement of Polycomb and Trithorax group complexes in the etiology of fetal alcohol spectrum disorders will undoubtedly enhance understanding of the role that epigenetic programming plays in this complex disorder.

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Available from: Kylee J Veazey, Jun 16, 2015
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    • "For the above reasons, we and others use avian embryos to study the etiology of ethanol-induced CHDs. The etiology of FAS and FASD has been the focus of much study, especially the cellular and molecular mechanisms (e.g., reviewed in Cole et al., 2012; Ungerer et al., 2013; Veazey et al., 2013). Ethanol exposure at gastrulation has been shown to alter the expression of critical proteins (e.g., transcription factors) within the avian cardiac mesoderm at stage 9, before the heart begins to function (Serrano et al., 2010). "
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    ABSTRACT: Disturbed cardiac function at an early stage of development has been shown to correlate with cellular/molecular, structural as well as functional cardiac anomalies at later stages culminating in the congenital heart defects (CHDs) that present at birth. While our knowledge of cellular and molecular steps in cardiac development is growing rapidly, our understanding of the role of cardiovascular function in the embryo is still in an early phase. One reason for the scanty information in this area is that the tools to study early cardiac function are limited. Recently developed and adapted biophotonic tools may overcome some of the challenges of studying the tiny fragile beating heart. In this chapter, we describe and discuss our experience in developing and implementing biophotonic tools to study the role of function in heart development with emphasis on optical coherence tomography (OCT). OCT can be used for detailed structural and functional studies of the tubular and looping embryo heart under physiological conditions. The same heart can be rapidly and quantitatively phenotyped at early and again at later stages using OCT. When combined with other tools such as optical mapping (OM) and optical pacing (OP), OCT has the potential to reveal in spatial and temporal detail the biophysical changes that can impact mechanotransduction pathways. This information may provide better explanations for the etiology of the CHDs when interwoven with our understanding of morphogenesis and the molecular pathways that have been described to be involved. Future directions for advances in the creation and use of biophotonic tools are discussed.
    Frontiers in Physiology 09/2014; 5:351. DOI:10.3389/fphys.2014.00351 · 3.53 Impact Factor
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    • "This model suggested combined genetic and environmental inhibition of PI3K/mTOR signaling for variability within FASD. Furthermore, Veazey et al., (2013) reported that exposure to alcohol alters the developmental trajectory of progenitor cells and compromises histogenesis. Thus ethanol can impair development by interfering with the molecular events regulating differentiation, whereas MTs regulate zincmediated transcriptional activation of genes involved in growth, proliferation, and differentiation (Sharma et al., 2013; Sharma and Ebadi 2014). "
    Alcohol Abuse:Prevalence, & Risk Management, Edited by Samuel Pombo, Filipe Borbosa, Marco Torrado, Nun Felix de Costa, 05/2014: chapter Fetal Alcohol Syndrome: Prevention, Diagnosis, & Treatment: pages 1-45; Nova Science Publishers.