Differential impact of MSX1 and MSX2 homeogenes on mouse maxillofacial skeleton

Abstract

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.