Msx1 Expression Regulation by Its Own Antisense RNA: Consequence on Tooth Development and Bone Regeneration

Abstract

Msx homeogenes play an important role in epithelial-mesenchymal interactions leading development. Msx1 is relevant for dental and craniofacial morphogenesis, as suggested by phenotypes of Msx1 mutations in human and Msx1 KO mice. During adulthood, Msx1 is still expressed in the skeleton where its role is largely unknown. Our group showed that the Msx1 gene is submitted to bidirectional transcription generating a long noncoding antisense (AS) RNA. During tooth development, Msx1 sense (S) and AS RNAs showed specific patterns of expression. Thus, the aim of the present study was to analyze the relation between Msx1 S and AS RNAs. In vivo mapping in adult mice showed that both Msx1 RNAs were detected in tested tissues such as bone. In vitro, Msx1 AS RNA decreased endogenous Msx1 S expression and modified Msx1 protein cell distribution. Regulations of Dlx5 and Bmp4 expression involving Msx1 S and AS RNAs showed that Msx1 AS RNA could modulate Msx1 function. The study of Msx1 S and AS RNA status is interesting in the case of tooth agenesis and bone loss to see if a disturbance of this balance could be associated with a disturbance of bone homeostasis. In that sense, our current results suggest a clear involvement of Msx1 in alveolar bone.

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“…35,36,39 Quagliata et al 40 demonstrated that lncRNA-HOTTIP positively regulates HOXA expression in HCC. The HOTTIP is located in physical contiguity with HOXA13 and directly controls the HOXA locus gene expression.…”

Making sense of Dlx1 antisense RNA

“…We are only beginning to understand possible mechanisms of how these ncRNAs might act on their targets, for example by impacting on sense RNA stability via sense-antisense duplex formation, targeting the sense transcript for degradation (for review see ). In recent years the function of a few lncRNAs in gene regulation has been demonstrated (Babajko et al, 2009;BlinWakkach et al, 2001;Feng et al, 2006;Lyle et al, 2000;Nagano et al, 2008;Sleutels et al, 2002).…”

“…Increasing evidence points to a role for non-coding RNAs (ncRNAs) in development and disease, a field rapidly gaining importance (Babajko et al, 2009;Berdal et al, 2002;Blin-Wakkach et al, 2001;Brockdorff et al, 1991;Chen and Carmichael, 2010;Clemson et al, 1996;Costa, 2010;Eberhart et al, 2008;Faghihi and Wahlestedt, 2009;Feng et al, 2006;Ginger et al, 2006;Gupta et al, 2010;Lipovich et al, 2010;Lyle et al, 2000;Nagano et al, 2008;Qureshi et al, 2010;Rinn et al, 2007;Sana et al, 2012;St Laurent et al, 2009;Young et al, 2005). NcRNAs include microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), with an emerging class of lncRNAs that act as endogenous riboregulators of transcription factors (TFs), including lncRNAs that directly bind TF proteins to regulate them (Chen and Carmichael, 2010;Costa, 2010;Hung and Chang, 2010;Hung et al, 2011;Kino et al, 2010;Lipovich et al, 2010;Martianov et al, 2007;Redon et al, 2010;Sana et al, 2012;.…”

Could lncRNAs be the Missing Links in Control of Mesenchymal Stem Cell Differentiation?

“…Given the important role of Msx1 in dental and craniofacial development, Msx1-as was shown to be and important osteogenic regulator, negatively affecting Msx1 transcript levels resulting in dose-dependent reduction of Msx1 protein levels (Babajko et al 2009, Berdal et al 2002). Moreover, the cellular location of Msx1 protein is modulated by Msx1-as and Msx1-as can abolish the inhibition of Dlx5 by Msx1.…”