Fibulin-5 deficiency causes developmental defect of premaxillary bone in mice

Abstract

Craniofacial sutures govern the shape of the craniofacial skeleton during postnatal development. The differentiation of suture mesenchymal cells to osteoblasts is precisely regulated in part by signaling through cell surface receptors that interact with extracellular proteins. Here we report that fibulin-5, a key extracellular matrix protein, is important for craniofacial skeletal development in mice. Fibulin-5 is deposited as a fibrous matrix in cranial neural crest-derived mesenchymal tissues, including craniofacial sutures. Fibulin-5-null mice show decreased premaxillary bone outgrowth during postnatal stages. While premaxillo-maxillary suture mesenchymal cells in fibulin-5-null mice were capable of differentiating into osteoblasts, suture cells in mutant mice were less proliferative. Our study provides the first evidence that fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis.

Widespread cis-regulatory convergence between the extinct Tasmanian tiger and gray wolf

“…FBLN5 enhances TGF beta-induced epithelial-to-mesenchymal transitions in mammary epithelial cells (Lee et al 2008), and deficiency is known to cause craniofacial phenotypes, including premaxillary bone defects. However, it is unclear whether this is mediated by its effects on TGF beta signaling (Noda et al 2015).…”

Creating diversity in mammalian facial morphology: a review of potential developmental mechanisms

“…In contrast to defects in facial process development that produce an extremely shortened face (see the previous section), defects in facial bone formation, which occur in later phases of facial development, lead to a shortened face with milder dysmorphology. For example, Fbln5 knockout mice exhibit decreased outgrowth of the premaxilla bones during postnatal stages, compared to control wild type mice [ 35 ]. Fibulin-5 is an extracellular matrix protein deposited as a fibrous matrix in neural crest-derived craniofacial suture mesenchyme and plays a role as a regulator of cellular function such as cell proliferation [ 35 , 36 ].…”

“…For example, Fbln5 knockout mice exhibit decreased outgrowth of the premaxilla bones during postnatal stages, compared to control wild type mice [ 35 ]. Fibulin-5 is an extracellular matrix protein deposited as a fibrous matrix in neural crest-derived craniofacial suture mesenchyme and plays a role as a regulator of cellular function such as cell proliferation [ 35 , 36 ]. While premaxilla-maxilla suture mesenchyme in Fbln5 knockout mice were capable of differentiating into osteoblasts, suture cells in the mutant were less proliferative, suggesting fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis [ 35 ].…”

“…Fibulin-5 is an extracellular matrix protein deposited as a fibrous matrix in neural crest-derived craniofacial suture mesenchyme and plays a role as a regulator of cellular function such as cell proliferation [ 35 , 36 ]. While premaxilla-maxilla suture mesenchyme in Fbln5 knockout mice were capable of differentiating into osteoblasts, suture cells in the mutant were less proliferative, suggesting fibulin-5 is indispensable for the regulation of facial suture mesenchymal cell proliferation required for craniofacial skeletal morphogenesis [ 35 ]. External facial morphology of adult Fbln5 knockout mice is almost normal, although facial length is slightly shortened compared to the control [ 35 ].…”

“…In mice, a shortened face without apparent facial bone defects is mainly brought about by a decrease in proliferation and differentiation of the ectomesenchyme which later differentiates into osteoblasts [ 35 ]. In addition, facial length variation observed in carnivorans and primates are correlated with the level of activity of Runx2 , which influences facial bone development duration [ 49 ].…”