Biology subjects

Pauws, E.

Publications and source records attributed to Pauws, E..

2 recordsLinked to original sources

bioRxiv2025

Chiari II brain malformation is secondary to open spina bifida

Chiari II brain malformation affects 90% of children with open spina bifida. Hindbrain herniation leads to hydrocephalus, together with higher brain anomalies including cerebral cortical defects implicated in learning disability, which affects 20-25% of children with spina bifida. The causal link between Chiari II and spina bifida has long been debated, and we aimed to determine whether Chiari II arises secondary to spina bifida, rather than as a separate effect of shared genetic or non-genetic factor(s). Pax3 gene function was conditionally deleted by Cdx2cre specifically in the lower body of mice, leaving the head genetically intact. Open spina bifida is seen in all Cdx2cre/+; Pax3fl/flfetuses, together with many features of Chiari II in the wild-type brain and skull. These include: hindbrain herniation, callosal and hippocampal hypogenesis, cortical thinning with neuronal heterotopia, a thickened ventricular zone, and posterior skull defects. Hence, the brain and skull defects of Chiari II arise secondary to open spina bifida, with likely disturbance of neurogenesis and neuronal migration early in gestation. The Cdx2cre/+; Pax3fl/fl mouse provides a model for improved understanding of Chiari II pathogenesis.

developmental biology↗

bioRxiv2021

The mechanobiology of craniosynostosis in Crouzon syndrome

Children with syndromic forms of craniosynostosis undergo a plethora of surgical interventions to resolve the clinical features caused by the premature fusion of cranial sutures. While surgical correction is reliable, the need for repeated rounds of invasive treatment puts a heavy burden on the child and their family. This study explores a non-surgical alternative using mechanical loading of the cranial joints to prevent or delay craniofacial phenotypes associated with Crouzon syndrome. We treated Crouzon syndrome mice before the onset of craniosynostosis by cyclical mechanical loading of cranial joints using a custom designed set-up. Cranial loading applied to the frontal bone partially restores normal skull morphology, significantly reducing the typical brachycephalic appearance. This is underpinned by the delayed closure of the coronal suture and of the intersphenoidal synchondrosis. This study provides a novel treatment alternative for syndromic craniosynostosis which has the potential to be an important step towards replacing, reducing or refining the surgical treatment of all craniosynostosis patients.

biophysics↗