The level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signaling

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26620%2F24%3APU151306" target="_blank" >RIV/00216305:26620/24:PU151306 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41467-024-46030-3" target="_blank" >https://www.nature.com/articles/s41467-024-46030-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-024-46030-3" target="_blank" >10.1038/s41467-024-46030-3</a>

Result language

angličtina

Original language name

The level of protein in the maternal murine diet modulates the facial appearance of the offspring via mTORC1 signaling

Original language description

The development of craniofacial skeletal structures is fascinatingly complex and elucidation of the underlying mechanisms will not only provide novel scientific insights, but also help develop more effective clinical approaches to the treatment and/or prevention of the numerous congenital craniofacial malformations. To this end, we performed a genome-wide analysis of RNA transcription from non-coding regulatory elements by CAGE-sequencing of the facial mesenchyme of human embryos and cross-checked the active enhancers thus identified against genes, identified by GWAS for the normal range human facial appearance. Among the identified active cis-enhancers, several belonged to the components of the PI3/AKT/mTORC1/autophagy pathway. To assess the functional role of this pathway, we manipulated it both genetically and pharmacologically in mice and zebrafish. These experiments revealed that mTORC1 signaling modulates craniofacial shaping at the stage of skeletal mesenchymal condensations, with subsequent fine-tuning during clonal intercalation. This ability of mTORC1 pathway to modulate facial shaping, along with its evolutionary conservation and ability to sense external stimuli, in particular dietary amino acids, indicate that the mTORC1 pathway may play a role in facial phenotypic plasticity. Indeed, the level of protein in the diet of pregnant female mice influenced the activity of mTORC1 in fetal craniofacial structures and altered the size of skeletogenic clones, thus exerting an impact on the local geometry and craniofacial shaping. Overall, our findings indicate that the mTORC1 signaling pathway is involved in the effect of environmental conditions on the shaping of craniofacial structures. Children's faces resemble their parents to various degrees. Here they show that the maternal diet affects the facial appearances of newborns and that inherited and adaptive mechanisms sculpturing facial bones are linked via dietary protein levels and the mTOR signaling pathway.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10700 - Other natural sciences

Project

<a href="/en/project/LQ1601" target="_blank" >LQ1601: CEITEC 2020</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

NATURE COMMUNICATIONS

ISSN

2041-1723

e-ISSN

—

Volume of the periodical

15

Issue of the periodical within the volume

March

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

1-15

UT code for WoS article

001191874200007

EID of the result in the Scopus database

2-s2.0-85188733299