Dataset Information

The epigenetic modifier Fam208a is required to maintain epiblast cell fitness.

ABSTRACT: Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epithelial-to-mesenchymal transition. Fam208a mutant epiblasts had increased expression of p53 pathway genes as well as several pluripotency-associated long non-coding RNAs. Fam208a mutants exhibited an increase in p53-driven apoptosis and complete removal of p53 could partially rescue their gastrulation block. This data demonstrates a new in vivo function of Fam208a in maintaining epiblast fitness, establishing it as an important factor at the onset of gastrulation when cells are exiting pluripotency.

SUBMITTER: Bhargava S

PROVIDER: S-EPMC5570896 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The epigenetic modifier Fam208a is required to maintain epiblast cell fitness.

Bhargava Shohag S Cox Brian B Polydorou Christiana C Gresakova Veronika V Korinek Vladimir V Strnad Hynek H Sedlacek Radislav R Epp Trevor Allan TA Chawengsaksophak Kallayanee K

Scientific reports 20170824 1

Gastrulation initiates with the formation of the primitive streak, during which, cells of the epiblast delaminate to form the mesoderm and definitive endoderm. At this stage, the pluripotent cell population of the epiblast undergoes very rapid proliferation and extensive epigenetic programming. Here we show that Fam208a, a new epigenetic modifier, is essential for early post-implantation development. We show that Fam208a mutation leads to impaired primitive streak elongation and delayed epitheli ...[more]

PMID: 28839193

Similar Datasets

Project description:Understanding the epigenetic role of microRNAs (miRNAs) has been a critical development in the field of neuropsychiatry and in understanding their underlying pathophysiology. Abnormalities in miRNA expression are often seen as key to the pathogenesis of many stress-associated mental disorders, including major depressive disorder (MDD). Recent advances in omics biology have further contributed to this understanding and expanded the role of miRNAs in networking a diverse array of molecular pathways, which are essentially related to the stress adaptivity of a healthy brain. Studies have highlighted the role of many such miRNAs in causing maladaptive changes in the brain's stress axis. One such miRNA is miR-218, which is debated as a critical candidate for increased stress susceptibility. miR-218 is expressed throughout the brain, notably in the hippocampus and prefrontal cortex (PFC). It is expressed at various levels through life stages, as seen by adolescent and adult animal models. Until now, a minimal number of studies have been conducted on human subjects to understand its role in stress-related abnormalities in brain circuits. However, several studies, including animal and cell-culture models, have been used to understand the impact of miR-218 on stress response and hypothalamic-pituitary-adrenal (HPA) axis function. So far, expression changes in this miRNA have been found to regulate signaling pathways such as glucocorticoid signaling, serotonergic signaling, and glutamatergic signaling. Recently, the developmental role of miR-218 has generated interest, given its increasing expression from adolescence to adulthood and targeting the Netrin-1/DCC signaling pathway. Since miR-218 expression affects neuronal development and plasticity, it is expected that a change in miR-218 expression levels over the course of development may negatively impact the process and make individuals stress-susceptible in adulthood. In this review, we describe the role of miR-218 in stress-induced neuropsychiatric conditions with an emphasis on stress-related disorders.

Dataset Information

The epigenetic modifier Fam208a is required to maintain epiblast cell fitness.

Publications

The epigenetic modifier Fam208a is required to maintain epiblast cell fitness.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets