ArticleBMC developmental biology2011
Histone deacetylase activity is necessary for left-right patterning during vertebrate development.
Article in BMC developmental biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Serotonin has early, cilia-independent roles in Xenopus left-right patterning.Disease models & mechanisms · 2013Pooled it
- Laterality defects are influenced by timing of treatments and animal model.Differentiation; research in biological diversity · 2012Pooled it
- Phenotypically Discordant Anomalies in Conjoined Twins: Quirks of Nature Governed by Molecular Pathways?Diagnostics (Basel, Switzerland) · 2023Review
- Expression and cilia associated localization of Histone deacetylases 6 inmicroPublication biology · 2023Article
- Global feather orientations changed by electric current.iScience · 2021Article
- Making and breaking symmetry in development, growth and disease.Development (Cambridge, England) · 2019Review
- Review
- WDR5 regulates left-right patterning via chromatin-dependent and -independent functions.Development (Cambridge, England) · 2018Article
- Histone deacetylase activity has an essential role in establishing and maintaining the vertebrate neural crest.Development (Cambridge, England) · 2018Article
- The bioelectric code: An ancient computational medium for dynamic control of growth and form.Bio Systems · 2018Review
- Bioelectric signaling in regeneration: Mechanisms of ionic controls of growth and form.Developmental biology · 2018Review
- Establishing the Embryonic Axes: Prime Time for Teratogenic Insults.Journal of cardiovascular development and disease · 2017Review
- Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form.Developmental neurobiology · 2017Review
- From cytoskeletal dynamics to organ asymmetry: a nonlinear, regulative pathway underlies left-right patterning.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2016Review
- Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen.Journal of anatomy · 2016Article
- Physiological controls of large-scale patterning in planarian regeneration: a molecular and computational perspective on growth and form.Regeneration (Oxford, England) · 2016Article
- The availability of the embryonic TGF-β protein Nodal is dynamically regulated during glioblastoma multiforme tumorigenesis.Cancer cell international · 2016Article
- On Having No Head: Cognition throughout Biological Systems.Frontiers in psychology · 2016Review
- Disrupting Foxh1-Groucho interaction reveals robustness of nodal-based embryonic patterning.Mechanisms of development · 2015Article
- Epigenetic Control of Macrophage Shape Transition towards an Atypical Elongated Phenotype by Histone Deacetylase Activity.PloS one · 2015Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundConsistent asymmetry of the left-right (LR) axis is a crucial aspect of vertebrate embryogenesis. Asymmetric gene expression of the TGFβ superfamily member Nodal related 1 (Nr1) in the left lateral mesoderm plate is a highly conserved step regulating the situs of the heart and viscera. In Xenopus, movement of maternal serotonin (5HT) through gap-junctional paths at cleavage stages dictates asymmetry upstream of Nr1. However, the mechanisms linking earlier biophysical asymmetries with this transcriptional control point are not known.
resultsTo understand how an early physiological gradient is transduced into a late, stable pattern of Nr1 expression we investigated epigenetic regulation during LR patterning. Embryos injected with mRNA encoding a dominant-negative of Histone Deacetylase (HDAC) lacked Nr1 expression and exhibited randomized sidedness of the heart and viscera (heterotaxia) at stage 45. Timing analysis using pharmacological blockade of HDACs implicated cleavage stages as the active period. Inhibition during these early stages was correlated with an absence of Nr1 expression at stage 21, high levels of heterotaxia at stage 45, and the deposition of the epigenetic marker H3K4me2 on the Nr1 gene. To link the epigenetic machinery to the 5HT signaling pathway, we performed a high-throughput proteomic screen for novel cytoplasmic 5HT partners associated with the epigenetic machinery. The data identified the known HDAC partner protein Mad3 as a 5HT-binding regulator. While Mad3 overexpression led to an absence of Nr1 transcription and randomized the LR axis, a mutant form of Mad3 lacking 5HT binding sites was not able to induce heterotaxia, showing that Mad3's biological activity is dependent on 5HT binding.
conclusionHDAC activity is a new LR determinant controlling the epigenetic state of Nr1 from early developmental stages. The HDAC binding partner Mad3 may be a new serotonin-dependent regulator of asymmetry linking early physiological asymmetries to stable changes in gene expression during organogenesis.
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