FGFR2 directs inhibition of WNT signaling to regulate anterior fontanelle closure during skull development.

The calvarial bones of the infant skull are linked by transient fibrous joints known as sutures and fontanelles, which are essential for skull compression during birth and expansion during postnatal brain growth. Genetic conditions caused by pathogenic variants in FGFR2, such as Apert, Pfeiffer, and Crouzon syndromes, result in calvarial deformities due to premature suture fusion and a persistently open anterior fontanelle (AF). In this study, we investigated how Fgfr2 regulates AF closure by leveraging mouse genetics and single-cell transcriptomics.

FGF Signaling Regulates Development of the Anterior Fontanelle.

The calvarial bones of the infant skull are connected by transient fibrous joints known as sutures and fontanelles, which are essential for reshaping during birth and postnatal growth. Genetic disorders such as Apert, Pfeiffer, Crouzon, and Bent bone dysplasia linked to variants often exhibit multi-suture craniosynostosis and a persistently open anterior fontanelle (AF). This study leverages mouse genetics and single-cell transcriptomics to determine how regulates closure of the AF closure and its transformation into the frontal suture during postnatal development.

Fibroblast growth factor 2.

Fibroblast Growth Factor 2 (FGF2), also known as basic fibroblast growth factor, is a potent stimulator of growth and differentiation in multiple tissues. Its discovery traces back over 50 years ago when it was first isolated from bovine pituitary extracts due to its ability to stimulate fibroblast proliferation. Subsequent studies investigating the genomic structure of FGF2 identified multiple protein isoforms, categorized as the low molecular weight and high molecular weight FGF2.

MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses.

Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses.

CaMKIIδ-mediated inflammatory gene expression and inflammasome activation in cardiomyocytes initiate inflammation and induce fibrosis.

Inflammation accompanies heart failure and is a mediator of cardiac fibrosis. CaMKIIδ plays an essential role in adverse remodeling and decompensation to heart failure. We postulated that inflammation is the mechanism by which CaMKIIδ contributes to adverse remodeling in response to nonischemic interventions.

5-Flurouracil disrupts nuclear export and nuclear pore permeability in a calcium dependent manner.

Regulation of nuclear transport is an essential component of apoptosis. As chemotherapy induced cell death progresses, nuclear transport and the nuclear pore complex (NPC) are slowly disrupted and dismantled. 5-Fluorouracil (5-FU) and the camptothecin derivatives irinotecan and topotecan, are linked to altered nuclear transport of specific proteins; however, their general effects on the NPC and transport during apoptosis have not been characterized.