Search

Msx homeogenes play an important role in the 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. Our group showed that Msx1 gene expression can be regulated by a bidirectional transcription generating long noncoding antisense (AS) RNA the expression which is linked to the Msx1 sense (S) RNA level. Thus, the aim of the present study was to analyze the synthesis of Msx1 (AS) RNA. In vivo Msx1 AS expression analysis showed that (i) the putative promoter sequence but not the transcribed sequence was important and necessary for its expression, (ii) 2 different areas of alveolar bone can be distinguished depending on Msx1 S and AS expression, and (iii) Msx1 presence was necessary for Msx1 AS RNA full expression. In silico analysis of the Msx1 AS putative promoter region showed the presence of 4 Msx response elements possibly involved in Msx1 regulation. Msx1 constitutes an example of a bidirectionally transcribed gene giving rise to an S/AS RNA pair included in the big and growing family of AS noncoding RNAs. Our results contribute to defining a link between Msx1 S and AS RNAs resulting in a fine-tuned regulatory loop of Msx1 expression. The significance of this finding is that disturbance of the balance between Msx1 S and AS RNA status may be associated with tooth agenesis and bone loss. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

For many years the molecular mechanisms governing bone morphogenetic protein 4 (Bmp4) expression in tooth bud mesenchyme could be explained by an uncomplicated model involving the interaction of the homeobox gene Msx1 and the paired domain gene Pax9 and a limited proximal promoter segment of Bmp4. New insights have led to major revisions, but we are still far from understanding the role of Msx1 and Pax9 in the complex processes that result in the expression of Bmp4 in the mesenchymal layer of the developing tooth bud. The objective of these studies was to gain further insight into the molecular relationship between Pax9, Msx1, and Bmp4 in dental mesenchyme and explore its association with nonsyndromic tooth agenesis in humans. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Craniofacial development involves a large number of genes involved in a complex time- and site-specific cascade of cellular crosstalk. Msx homeobox genes are expressed very early and have been implicated in multiple signaling processes. However, little is known about their role in postnatal growth and at adult stages. The aim of this study was to compare the patterns of expression of Msx1 and Msx2 during postnatal growth and homeostasis. We used transgenic mice with a knock-in for Msx1 or Msx2. Msx expression was analyzed on whole-mount experiments on heterozygous mice. The results were confirmed by quantitative RT-PCR on mandible and tibia samples. Steady-state levels of Msx2 mRNA were determined at 2 ages, at postnatal day 14 and after 3 months, corresponding to phases of growth and homeostasis, respectively. Consistent with previous findings, the expression profiles of Msx1 and Msx2 overlapped during embryonic development. By contrast, marked differences in the patterns of expression of these 2 genes were observed during the growth phase. Msx1 was found to be expressed in basal bone during postnatal growth. Msx1 was not expressed in alveolar bone, whereas Msx2 was strongly and continually expressed. Msx2 was present in all growth plate cartilages, as previously shown for Msx1. Autopods displayed different patterns of expression during the mouse life cycle, with continuous expression of Msx1 only. Interestingly, both secretory cells (osteoblasts) and cells involved in bone resorption (osteoclasts) were found to be involved in Msx molecular pathways, their precise involvement depending on the anatomical site. The observed patterns correspond to specific sites during growth and constitute landmarks in our understanding of growth-related oral facial dysmorphologies. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]