Temporal-spatial expression of E-cadherin and FGF-2 in neural crest derived fusing cranial sutures

Abstract

Abstract Introduction: Understanding cranial suture developmental biology is important in elucidating the pathogenesis of craniosynostosis. Although recent studies in cranial suture biology have focused on growth factors and transcription factors, few have investigated adhesion molecules and the role they may play in cell migration and bone formation. Methods: RNA were extracted from posterior frontal (PF) fusing suture complexes from mice at serial time-points (p1, p3, p5, p7, p9, p11, p13, p15, p25 and p35) and were used to generate cDNA for microarray and quantitative real-time (qRT) PCR analysis. We performed a focused analysis of cell adhesion molecules. In addition, time-matched calvaria were analyzed for morphometric analysis, H&E staining, and immunohistochemistry. Results: Our microarray data revealed an over 4 fold increase in expression of E-cadherin, a cell-cell adhesion molecule and an osteoblast differentiation marker, in the PF sutures, compared to that of SAG suture during fusion. This differential expression was confirmed by qRT PCR. Expression of E-cahderin was preceded by an increased expression of FGF-2 two days earlier. FGF-2 stimulation is known to promote skeletogenic differentiaion of premigratory neural crest cells (NCC) and increase E-cadherin expression in osteoblasts. Immunohistochemistry reveals an increase expression of E-cadherin in PF suture at the osteogenic fronts during fusion in areas of cell gathering. Conclusions: Here we describe E-cadherin and FGF-2 temporal-spatial expression pattern in the neural crest derived fusing PF suture. This may add insight into the role cadherins may play in syndromic forms of craniosynostosis associated with FGFR gain-of-function mutations.