BBS9 gene in nonsyndromic craniosynostosis: Role of the primary cilium in the aberrant ossification of the suture osteogenic niche

Marta Barba, Lorena Di Pietro, Luca Massimi, Maria Concetta Geloso, Paolo Frassanito, Massimo Caldarelli, Fabrizio Michetti, Stefano Della Longa, Paul A. Romitti, Concezio Di Rocco, Alessandro Arcovito, Ornella Parolini, Gianpiero Tamburrini, Camilla Bernardini, Simeon Boyd, Wanda Lattanzi

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Nonsyndromic craniosynostosis (NCS) is the premature ossification of skull sutures, without associated clinical features. Mutations in several genes account for a small number of NCS patients; thus, the molecular etiopathogenesis of NCS remains largely unclear. Our study aimed at characterizing the molecular signaling implicated in the aberrant ossification of sutures in NCS patients. Comparative gene expression profiling of NCS patient sutures identified a fused suture-specific signature, including 17 genes involved in primary cilium signaling and assembly. Cells from fused sutures displayed a reduced potential to form primary cilia compared to cells from control patent sutures of the same patient. We identified specific upregulated splice variants of the Bardet Biedl syndrome-associated gene 9 (BBS9), which encodes a structural component of the ciliary BBSome complex. BBS9 expression increased during in vitro osteogenic differentiation of suture-derived mesenchymal cells of NCS patients. Also, Bbs9 expression increased during in vivo ossification of rat sutures. BBS9 functional knockdown affected the expression of primary cilia on patient suture cells and their osteogenic potential. Computational modeling of the upregulated protein isoforms (observed in patients) predicted that their binding affinity within the BBSome may be affected, providing a possible explanation for the aberrant suture ossification in NCS.

Original languageEnglish (US)
Pages (from-to)58-70
Number of pages13
StatePublished - Jul 1 2018


  • BBS9
  • Gene expression signatures
  • Innovative biotechnologies
  • Mesenchymal stromal cells
  • Nonsyndromic craniosynostosis
  • Primary cilium

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology


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