Cranial Neural Crest Cells and Their Role in the Pathogenesis of Craniofacial Anomalies and Coronal Craniosynostosis

Abstract

Craniofacial anomalies are among the most common of birth defects. The pathogenesis of craniofacial anomalies frequently involves defects in the migration, proliferation, and fate of neural crest cells destined for the craniofacial skeleton. Genetic mutations causing deficient cranial neural crest migration and proliferation can result in Treacher Collins syndrome, Pierre Robin sequence, and cleft palate. Defects in post-migratory neural crest cells can result in pre- or post-ossification defects in the developing craniofacial skeleton and craniosynostosis (premature fusion of cranial bones/cranial sutures). The coronal suture is the most frequently fused suture in craniosynostosis syndromes. It exists as a biological boundary between the neural crest-derived frontal bone and paraxial mesoderm-derived parietal bone. The objective of this review is to frame our current understanding of neural crest cells in craniofacial development, craniofacial anomalies, and the pathogenesis of coronal craniosynostosis. We will also discuss novel approaches for advancing our knowledge and developing prevention and/or treatment strategies for craniofacial tissue regeneration and craniosynostosis.

Epidemiology of Pierre‐Robin sequence in Europe: A population‐based EUROCAT study

“…There have been a number of theories developed to explain the pathogenesis of PRS, but the most prevailing is that during embryonic development, intrinsic and/or extrinsic factors lead to micrognathia, which in turn causes failure of the tongue to drop from between the palatal shelves resulting in most cases in cleft palate. Recent studies show that micrognathia in PRS is primarily due to neural crest developmental abnormalities caused by defects in the migration, proliferation, and survival of cranial neural crest cells and their derivatives 8 . The PRS is thought to be due to diminished signalling in cranial neural crest cells leading to reduced proliferation and/or osteogenesis within the mandible 9,10 .…”

Cranial Suture Mesenchymal Stem Cells: Insights and Advances

“…Currently, the only applicable therapeutic option for craniosynostosis is complex surgery, for instance, spring-mediated cranioplasty and minimally invasive strip craniectomy partial craniectomy followed by cranial molding orthosis (helmet) therapy, to correct the deformity and prevent its devastating sequelae [23,24], which are most likely to occur if appropriate surgical intervention is not conducted in time [24]. Numerous published studies have shown that craniosynostosis is associated with TWIST1 mutation and FGFR mutation [18,20,25], and also relates to the premature loss of SuSCs [26], which perturbs the production of sufficient undifferentiated mesenchymal cells to maintain the suture patent [1]. More importantly, the aforementioned four distinctive markers of SuSCs also have a strong relationship with craniosynostosis.…”

Tissue-Nonspecific Alkaline Phosphatase—A Gatekeeper of Physiological Conditions in Health and a Modulator of Biological Environments in Disease

“…Moreover, the suture comprises several specific stem cell populations that are spatially organized over time and differentially contribute to the suture closure process [ 124 , 125 ]. Neural crest-derived cells are reported to be more proliferative and osteogenic within activated Wnt and FGF signaling domains, and both types also mutually influence each other [ 126 ]. They were shown to more readily produce mineralization nodules in comparison with mesenchyme-derived cells, possibly indicating that they can take over the lead in the suture milieu in case of altered osteogenic differentiation, thereby supporting craniosynostosis [ 127 ].…”