Foxe1 has conserved functions in development of the craniofacial skeleton

Date of news: 13 March 2023

A joint initiative between researchers at RIBES and Radboudumc has led to new insights into the functions of a gene that in humans is implicated in cleft palate and thyroid dysgenesis. A zebrafish mutant was generated that has a disruption in the nuclear localization signal in the foxe1 gene. Skeletal development and thyroidogenesis in these mutants were investigated, focusing on embryonic and larval stages.


The findings, published in Frontiers of Cell and Developmental Biology, highlight the conserved role of Foxe1 in skeletal development and thyroidogenesis, and show differential signaling of osteogenic and chondrogenic genes related to foxe1 mutation.

Sophie Raterman, the PhD student who performed the work says: “In the mutant fish we compare the skeletal development with that of normal fish. We do that when they are five days old. The zebrafish are still transparent at this age, so by staining we can see through the soft tissues and identify minor malformations in the skeletal formation process. If we have more knowledge of the early development of the (facial) skeleton, we will also have a better understanding of which environmental factors can influence deviations from this."

The implications of the work go beyond translational value - as skeletal development is a very delicate process in which gene-environment interactions determine how it unfolds. “Molecular techniques allow us to find out what causes the malformations. This provides important information about the complex processes behind the formation of the skeleton. If something goes wrong early in the development, this has consequences for the rest of life, for example for food intake or swimming behaviour.”