Epigenetic regulation of face formation

March 30, 2017, Friedrich Miescher Institute for Biomedical Research
Epigenetic regulation of face formation
Credit: jazzia / 123RF Stock Photo

Each face is unique, even though the genes controlling facial shape are almost identical in every individual. Filippo Rijli and his team at the Friedrich Miescher Institute for Biomedical Research (FMI) have discovered an epigenetic mechanism that regulates face morphogenesis. During early development, the neural crest cells that give rise to the various facial structures maintain chromatin plasticity, with all the genes involved remaining poised to respond to local cues. Once the cells are exposed to these environmental signals, a switch from a poised to an active chromatin state occurs, inducing position specific transcriptional programs that give rise to the chin, cheekbones or forehead.

A pronounced forehead, a button nose, high cheekbones or almond-shaped eyes – each face is unique, despite the fact that the controlling the shape of craniofacial structures are almost identical in every individual. So how do these distinctive features arise from the same subset of genes?

The generation of distinctly shaped craniofacial structures assembled into a harmonious face depends on a specialized cell type – , which give rise to most of the skull and face cartilage and bones. During early embryonic development, the neural migrate from the developing neural tube to the prospective head region. Premigratory neural crest cells are naive multipotent cells, which become committed to a cartilaginous fate once they reach their final destination.

Neural crest cells also acquire specific "positional" identities (related to their position in the developing face), which define the shapes of the bones and cartilage that will form the mandible and chin, cheekbones, nose or forehead. This positional identity is acquired during the cells' migration, depending on the path taken and their interactions with the local environment. However, even after migration, positional identity is not irreversibly fixed, and neural crest cells maintain a degree of plasticity.

To date, it has not been clear how neural crest cells can maintain plasticity through migration, while being poised to respond to local cues and induce position-specific transcriptional programs.

Filippo Rijli and his group at the FMI, together with FMI computational biologist Michael Stadler, have now elucidated how this process is enabled by epigenetic regulation of chromatin organization.

In a study published in Science, they describe a specific chromatin organization whereby neural crest cells remain transcriptionally poised until the end of their migration, thus maintaining the potential to give rise to all the different facial elements, irrespective of their final position.

First author Maryline Minoux, a visiting scientist in the Rijli lab and professor at the Strasbourg University Faculty of Dental Medicine, explains: "We compared the chromatin profile of subpopulations of neural crest cells in different positions before and after migration. In the postmigratory neural crest cells, the promoters of the differentially silenced genes – i.e. genes not expressed in some populations, but expressed in others – were maintained in a bivalent configuration marked by both repressive H3K27me3 and activating H3K4me2 epigenetic histone modifications. These genes were thus poised for activation. Surprisingly, this poised configuration was already present in the premigratory neural crest cells." Once the cells receive specific environmental signals, they lose the repressive H3K27me3 mark and start the position-specific transcriptional program.

In addition, the authors found that the poised chromatin state is regulated by the Ezh2 component of the Polycomb Repressive Complex 2, a known remodeler during embryonic development. Ezh2 specifically adds methyl groups to lysine 27 of histone H3.

Rijli comments: "This is a novel conceptual framework for understanding how different facial features arise. Epigenetic poising may allow cranial neural crest cells to rapidly adapt their response to local variations in environmental signaling, thus potentially explaining differences in facial shape between individuals."

Explore further: Scientists transform lower-body cells into facial cartilage

More information: Minoux M, Holwerda S, Vitobello A, Kitazawa T, Kohler H, Stadler MB, Rijli FM, (2017) Gene bivalency at polycomb domains regulates cranial neural crest positional identity. Science advance online publication, science.sciencemag.org/cgi/doi … 1126/science.aal2913

Related Stories

Scientists transform lower-body cells into facial cartilage

June 27, 2016
Caltech scientists have converted cells of the lower-body region into facial tissue that makes cartilage, in new experiments using bird embryos. The researchers discovered a "gene circuit," composed of just three genes, that ...

YAP protein plays a crucial role in the development of the human neural crest

March 22, 2016
To grow or to specialise? To remain stationary or initiate migration? How do cells know what to do and how they should develop? The Hippo/YAP signalling pathway plays a crucial role when the cells of the neural crest – ...

Scientists ID key fetal cells vulnerable to Zika

September 29, 2016
(HealthDay)—The devastating mosquito-borne Zika virus can infect cells that play a role in skull development, a new study finds.

Recommended for you

Psychiatric disorders share an underlying genetic basis

June 21, 2018
Psychiatric disorders such as schizophrenia and bipolar disorder often run in families. In a new international collaboration, researchers explored the genetic connections between these and other disorders of the brain at ...

Deep data dive helps predict cerebral palsy

June 21, 2018
When University of Delaware molecular biologist Adam Marsh was studying the DNA of worms living in Antarctica's frigid seas to understand how the organisms managed to survive—and thrive—in the extremely harsh polar environment, ...

Genetic variation in progesterone receptor tied to prematurity risk, study finds

June 21, 2018
Humans have unexpectedly high genetic variation in the receptor for a key pregnancy-maintaining hormone, according to research led by scientists at the Stanford University School of Medicine. The finding may help explain ...

Shared genetics may shape treatment options for certain brain disorders

June 20, 2018
Symptoms of schizophrenia and bipolar disorder, including psychosis, depression and manic behavior, have both shared and distinguishing genetic factors, an international consortium led by researchers from Vanderbilt University ...

Scientists unravel DNA code behind rare neurologic disease

June 20, 2018
Scientists conducting one of the largest full DNA analyses of a rare disease have identified a gene mutation associated with a perplexing brain condition that blinds and paralyzes patients.

Simple sugar delays neurodegeneration caused by enzyme deficiency

June 20, 2018
A new therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB). Neurodegeneration in this condition results from the abnormal accumulation of essential cellular ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.