A cleft lip or palate arises from the combined effects of genes and inflammatory risk factors experienced during pregnancy, such as smoking or infections, finds a new study.
The study, published in Nature Communications, has revealed for the first time how genetic and environmental factors come together to form a cleft lip or palate in a developing foetus.
Cleft lip, with or without cleft palate, is the most common craniofacial malformation seen at birth, affecting one in 700 live births. It can have devastating consequences for babies and their families, as the infants may experience difficulty feeding, speaking, and hearing, and may be at increased risk for ear infections and dental problems.
Senior author said: “It has been known for some time that there is a genetic component to cleft lip, and that some environmental factors such as smoking, stress, infections and malnutrition during pregnancy can also increase the risk of cleft lip. Here, for the first time we have shown how these two factors work together, and why both genetic and environmental risk factors are necessary for a child to be born with cleft lip.”
The researchers were studying families who carry mutations in the e-cadherin gene, which is known to be implicated in cleft lip, but noted that not everyone with the mutation develops a cleft lip. They reproduced this mutation in mice and frogs, which generated malformations similar to the cleft lip in humans, but only when the mice and frogs carrying the mutation were also exposed to inflammation-causing environmental factors. The researchers also found similar effects in human stem cells with both the mutation and inflammation.
The e-cadherin protein plays a role in foetal development, as neural crest cells – the embryonic stem cells that form facial features – move together to form the face. In normal development, the neural crest cells migrate together in two halves, wrapping around the head, before joining together to form the face. This requires e-cadherin to act as a glue between cells. If the two halves of the neural crest cells do not fully bind together, the infant will be born with a cleft lip or palate.
The mutation identified by the researchers reduces the production of the e-cadherin protein, as DNA methylation reduces transcription, but they found that the mutation alone did not reduce e-cadherin levels enough to cause a cleft lip. It was only when a foetus with the mutation was also exposed to environmental risk factors that drive inflammation throughout the body (which can include smoking, stress, malnutrition or infections), that DNA methylation was increased and e-cadherin levels were too low for the neural crest cells to bind themselves together to fully form the lip and palate.
First author said: “Our study is the first to demonstrate in detail how genetic and environmental factors combine to cause a birth defect, while it is also a noteworthy example of epigenetics, as environmental factors influence the expression of a gene.”
The researchers hope that their findings will contribute to the development of new treatments or preventative strategies for cleft lip or palate, and clarify the risk factors to help people reduce the chance their baby will develop the condition.
The senior author said: “Testing for this mutation could be a straightforward part of antenatal care, so that if someone carries the mutation, they would be advised to take steps to reduce the risk of inflammation that could combine with the genetic factor to result in a cleft lip. In addition to targeting factors such as smoking, the prescription of anti-inflammatory drugs may also help for at-risk pregnant women.”
https://www.nature.com/articles/s41467-023-38526-1
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fneural-crest-e-cadherin&filter=22
Cleft lip caused by combination of genes and environment
- 1,856 views
- Added
Edited
Latest News
How the brain fine-tunes it…
By newseditor
Posted 25 Apr
Immune cells carry a long-l…
By newseditor
Posted 25 Apr
Mutations in noncoding DNA…
By newseditor
Posted 24 Apr
More influence of environme…
By newseditor
Posted 24 Apr
The assembly of the human c…
By newseditor
Posted 24 Apr
Other Top Stories
Prognostic biomarker found in ovarian cancer patients
Read more
Identical driver gene mutations found in metastatic cancers
Read more
How a sleeping cancer awakens and metastasizes
Read more
Cancer increases glucose supply by hijacking microbiome!
Read more
"Check Point Theory" to treat cancer wins 2018 Nobel Prize in Physi…
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
The MYCN 50 UTR as a therap…
By newseditor
Posted 25 Apr
Control of neuronal excitat…
By newseditor
Posted 25 Apr
Epithelial UNC-23 limits me…
By newseditor
Posted 25 Apr
Macrophage memories of earl…
By newseditor
Posted 25 Apr
A gut-derived hormone regul…
By newseditor
Posted 25 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar