Bone Fusion in Normal and Pathological Development is Constrained by the Network Architecture of the Human Skull

Abstract

Craniosynostosis, the premature fusion of cranial bones, affects the correct development of the skull producing morphological malformations in newborns. To assess the susceptibility of each craniofacial articulation to close prematurely, we used a network model of the skull to quantify the link reliability (an index based on stochastic block models and Bayesian inference) of each articulation. We show that, of the 93 human skull articulations at birth, the few articulations that are associated with non-syndromic craniosynostosis conditions have statistically significant lower reliability scores than the others. In a similar way, articulations that close during the normal postnatal development of the skull have also lower reliability scores than those articulations that persist through adult life. These results indicate a relationship between the architecture of the skull and the specific articulations that close during normal development as well as in pathological conditions. Our findings suggest that the topological arrangement of skull bones might act as a structural constraint, predisposing some articulations to closure, both in normal and pathological development, also affecting the long-term evolution of the skull.

Evolutionary phenome-genome analysis of cranial suture closure in mammals

“…Our evolutionary analysis shows that the patency of a suture depends also on the patency of other 1 7 1 sutures, following the most common anteroposterior order of ossification of the skull in mammals 1 7 2 (Koyabu et al, 2011(Koyabu et al, , 2014. This result agrees with recent theoretical findings proposing that the 1 7 3 1 2 organization of the skull, as a network of bones connected by sutures, can bias suture closure 1 7 4 (Esteve-Altava et al, 2017;Esteve-Altava & Rasskin-Gutman, 2015). For example, by directing 1 7 5 mechano-transduction and morphogenetic signals (Khonsari et al, 2013;Katsianou et al, 2016).…”

Signaling Mechanisms Underlying Genetic Pathophysiology of Craniosynostosis

“…Craniosynostosis is the premature fusion of one or more cranial sutures, which is the second most common craniofacial anomalies, just listed behind oralfacial clefts 5, 6. In a majority of cases, craniosynostosis expresses as an isolated and nonsyndromic disease, which composed about 85% of all cases 7.…”

Quantitative study of the primary ossification centre of the parietal bone in the human fetus

“…The mean coronal diameter of the parietal primary ossification center in the gestational age range of 18-30 weeks was between 24.60 ± 0.03 mm and 41.97 ± 0.38 mm on the right, and between 25.51 ± 0.01 mm and 42.13 ± 0.95 mm on the left, following the quartic function: y = 21.746 + 0.000025 × (age) 4 ± 1.256 (R 2 = 0.95) -(Fig. 3A).…”

“…In the human prenatal period is indispensably to assess in utero the fetal skull by routine ultrasound. Abnormalities of the parietal bone development may involve the following defects: craniosynostosis, cranium bifidum, fusion of the parietal foramina, congenital absence of the skull roof, anencephaly or exencephaly [4,5,10,13].…”