TGF-??1, FGF-2, and Receptor mRNA Expression in Suture Mesenchyme and Dura versus Underlying Brain in Fusing and Nonfusing Mouse Cranial Sutures

Abstract

Recent studies have supported a functional role for the transforming growth factor beta-1 (TGF-beta1) and fibro-blast growth factor 2 (FGF-2) signaling cascades in the process of mouse cranial suture fusion. TGF-beta1 and FGF-2 protein expression have been shown to be elevated in the fusing posterior frontal suture versus the nonfusing sagittal suture. The authors evaluated simultaneous mRNA expression of TGF-beta1 and its R1 receptor and FGF-2 and its R2 receptor during mouse cranial suture fusion. They evaluated the suture mesenchyme-dura complex separately from the underlying brain to determine whether there is tissue-specific biologic activity (i.e., brain versus suture mesenchyme-dura) for each cytokine and receptor. Data were collected from 150 male CD-1 mice studied over five time periods from postnatal days 22 to 45. They utilized reverse-transcriptase polymerase chain reaction as a means to detect TGF-beta1, TGF-beta receptor 1 (TGF-betaR1), FGF-2, and FGF receptor 2 (FGFR2) mRNA expression in mouse cranial tissues, beginning with the period of initiation of posterior frontal cranial suture fusion (postnatal day 22) and extending through completion of posterior frontal suture fusion (postnatal day 45). Expression of FGF-2 was significantly greater in posterior frontal suture mesenchyme and dura compared with sagittal suture mesenchyme and dura during the period of initiation of posterior frontal suture fusion, localizing this cytokine's expression to posterior frontal suture mesenchyme and dura during the process of cranial suture fusion. TGF-beta1 and FGFR2 mRNA expression was found to be up-regulated in posterior frontal suture mesenchyme and dura relative to the underlying brain tissue throughout the study period, whereas TGF-betaR1 and FGF-2 mRNA expression was significantly elevated relative to the underlying brain only at time points corresponding to the initiation of posterior frontal suture fusion (between postnatal days 22 and 31). These results indicate that there is tissue-specific mRNA expression of TGF-beta1, FGF-2, and their receptors between suture mesenchyme and dura and the underlying brain, which correlates with the period of posterior frontal suture fusion in the mouse model. Differences in gene expression between suture mesenchyme and dura relative to the underlying brain may be an important regulator of cranial suture biology. Understanding these differences may eventually help to identify possible targets and time windows by which to most effectively modulate cranial suture fusion.