Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
DNA methylation is a major epigenetic modification; however, the precise role of DNA methylation in vertebrate development is still not fully understood. Here, we show that DNA methylation is essential for the establishment of the left-right (LR) asymmetric body plan during vertebrate embryogenesis. Perturbation of DNA methylation by depletion of DNA methyltransferase 1 (dnmt1) or dnmt3bb.1 in zebrafish embryos leads to defects in dorsal forerunner cell (DFC) specification or collective migration, laterality organ malformation, and disruption of LR patterning. Knockdown of dnmt1 in Xenopus embryos also causes similar defects. Mechanistically, loss of dnmt1 function induces hypomethylation of the lefty2 gene enhancer and promotes lefty2 expression, which consequently represses Nodal signaling in zebrafish embryos. We also show that Dnmt3bb.1 regulates collective DFC migration through cadherin 1 (Cdh1). Taken together, our data uncover dynamic DNA methylation as an epigenetic mechanism to control LR determination during early embryogenesis in vertebrates.
Amack,
The T box transcription factor no tail in ciliated cells controls zebrafish left-right asymmetry.
2004, Pubmed
Amack,
The T box transcription factor no tail in ciliated cells controls zebrafish left-right asymmetry.
2004,
Pubmed
Anderson,
Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration.
2009,
Pubmed
Blum,
Xenopus, an ideal model system to study vertebrate left-right asymmetry.
2009,
Pubmed
,
Xenbase
Blum,
The evolution and conservation of left-right patterning mechanisms.
2014,
Pubmed
,
Xenbase
Blum,
Ciliation and gene expression distinguish between node and posterior notochord in the mammalian embryo.
2007,
Pubmed
,
Xenbase
Burdine,
Conserved and divergent mechanisms in left-right axis formation.
2000,
Pubmed
Campos,
Molecular evolution of zebrafish dnmt3 genes and thermal plasticity of their expression during embryonic development.
2012,
Pubmed
Chen,
Spatial transcriptomic analysis of cryosectioned tissue samples with Geo-seq.
2017,
Pubmed
Choi,
Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430.
2007,
Pubmed
Chung,
Intra-endodermal interactions are required for pancreatic beta cell induction.
2008,
Pubmed
Dai,
TET-mediated DNA demethylation controls gastrulation by regulating Lefty-Nodal signalling.
2016,
Pubmed
Dunican,
xDnmt1 regulates transcriptional silencing in pre-MBT Xenopus embryos independently of its catalytic function.
2008,
Pubmed
,
Xenbase
Farooq,
Histone deacetylase 3 (hdac3) is specifically required for liver development in zebrafish.
2008,
Pubmed
Feldman,
Lefty antagonism of Squint is essential for normal gastrulation.
2002,
Pubmed
Ghoshal,
5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal.
2005,
Pubmed
Guo,
The DNA methylation landscape of human early embryos.
2014,
Pubmed
Hamada,
Establishment of vertebrate left-right asymmetry.
2002,
Pubmed
Hirokawa,
Nodal flow and the generation of left-right asymmetry.
2006,
Pubmed
Jiang,
Sperm, but not oocyte, DNA methylome is inherited by zebrafish early embryos.
2013,
Pubmed
Kimelman,
Mesoderm induction: from caps to chips.
2006,
Pubmed
,
Xenbase
Kimmel,
Stages of embryonic development of the zebrafish.
1995,
Pubmed
,
Xenbase
Kinder,
The organizer of the mouse gastrula is composed of a dynamic population of progenitor cells for the axial mesoderm.
2001,
Pubmed
Kumaki,
QUMA: quantification tool for methylation analysis.
2008,
Pubmed
Li,
MethPrimer: designing primers for methylation PCRs.
2002,
Pubmed
Long,
The zebrafish nodal-related gene southpaw is required for visceral and diencephalic left-right asymmetry.
2003,
Pubmed
Matsui,
Canopy1, a positive feedback regulator of FGF signaling, controls progenitor cell clustering during Kupffer's vesicle organogenesis.
2011,
Pubmed
Matsui,
Left-right asymmetry in zebrafish.
2012,
Pubmed
Matsui,
Cell collectivity regulation within migrating cell cluster during Kupffer's vesicle formation in zebrafish.
2015,
Pubmed
McGrath,
Two populations of node monocilia initiate left-right asymmetry in the mouse.
2003,
Pubmed
Nonaka,
Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein.
1998,
Pubmed
Okada,
Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination.
2005,
Pubmed
Oteiza,
Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ.
2010,
Pubmed
Oteíza,
Origin and shaping of the laterality organ in zebrafish.
2008,
Pubmed
Peeters,
Human laterality disorders.
2006,
Pubmed
Potok,
Reprogramming the maternal zebrafish genome after fertilization to match the paternal methylation pattern.
2013,
Pubmed
Rai,
Zebra fish Dnmt1 and Suv39h1 regulate organ-specific terminal differentiation during development.
2006,
Pubmed
Ruzov,
Kaiso is a genome-wide repressor of transcription that is essential for amphibian development.
2004,
Pubmed
,
Xenbase
Schier,
Molecular genetics of axis formation in zebrafish.
2005,
Pubmed
Schweickert,
Cilia-driven leftward flow determines laterality in Xenopus.
2007,
Pubmed
,
Xenbase
Schötz,
Quantitative differences in tissue surface tension influence zebrafish germ layer positioning.
2008,
Pubmed
Shimoda,
Identification of a gene required for de novo DNA methylation of the zebrafish no tail gene.
2005,
Pubmed
Smith,
DNA methylation: roles in mammalian development.
2013,
Pubmed
Stainier,
Zebrafish genetics and vertebrate heart formation.
2001,
Pubmed
Tam,
Gene function in mouse embryogenesis: get set for gastrulation.
2007,
Pubmed
Tanaka,
FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination.
2005,
Pubmed
Wang,
Programming and inheritance of parental DNA methylomes in mammals.
2014,
Pubmed
Wang,
Fev regulates hematopoietic stem cell development via ERK signaling.
2013,
Pubmed
Wang,
Epigenetic regulation of left-right asymmetry by DNA methylation.
2017,
Pubmed
,
Xenbase
Wei,
Ncor2 is required for hematopoietic stem cell emergence by inhibiting Fos signaling in zebrafish.
2014,
Pubmed
Zhang,
Eph/ephrin signaling maintains the boundary of dorsal forerunner cell cluster during morphogenesis of the zebrafish embryonic left-right organizer.
2016,
Pubmed
