Abstract
BackgroundThe mammalian esophageal musculature is unique in that it makes a transition from smooth to skeletal muscle, with most of this process occurring after birth. In order to better understand the mechanisms that control esophageal musculature development, we investigated the roles in this process of the paired box transcription factor, PAX7, a principal regulator of skeletal myogenic progenitor cells. Previous studies showed that Pax7 is important for determining the esophageal muscle composition.ResultsWe characterized the postnatal development of the esophageal musculature in Pax7−/− mice by analyzing morphology, muscle composition, and the expression of markers of myogenesis, cell proliferation, and apoptosis. Pax7−/− mice displayed megaesophagus with a severe defect in the postnatal developmental process whereby esophageal smooth muscle is replaced by skeletal muscle. Pax7−/− esophagi have substantially reduced skeletal muscle, most likely due to diminished proliferation and premature differentiation of skeletal muscle precursor cells. This impaired the proximal-to-distal progression of skeletal myogenesis and indirectly affected the patterning of the smooth muscle-containing portion of the esophageal musculature.ConclusionsPostnatal patterning of the esophageal musculature appears to require robust, PAX7-dependent cell proliferation to drive the proximal-to-distal progression of skeletal myogenesis. This process in turn influences distal smooth muscle morphogenesis and development of the mature pattern of the esophageal musculature.Electronic supplementary materialThe online version of this article (doi:10.1186/s13395-015-0068-0) contains supplementary material, which is available to authorized users.
Highlights
The mammalian esophageal musculature is unique in that it makes a transition from smooth to skeletal muscle, with most of this process occurring after birth
We showed that mice lacking the multifunctional cell surface receptor Cdo have a defect in the postnatal developmental process whereby esophageal smooth muscle is replaced by skeletal muscle
Most smooth muscle in the esophagi of Pax7+/− mice was found in a short, broad segment at the esophagogastric junction, where smooth muscle cell (SMC) were bundled into fascicles that were stacked side by side with an orientation perpendicular to the lumen (Fig. 1i)
Summary
The mammalian esophageal musculature is unique in that it makes a transition from smooth to skeletal muscle, with most of this process occurring after birth. Results: We characterized the postnatal development of the esophageal musculature in Pax7−/− mice by analyzing morphology, muscle composition, and the expression of markers of myogenesis, cell proliferation, and apoptosis. Pax7−/− esophagi have substantially reduced skeletal muscle, most likely due to diminished proliferation and premature differentiation of skeletal muscle precursor cells. This impaired the proximal-to-distal progression of skeletal myogenesis and indirectly affected the patterning of the smooth muscle-containing portion of the esophageal musculature. The lower esophageal sphincter (LES) is a bundle of smooth muscles at the distal end of the esophagus, where it meets the stomach. Tonic smooth muscles of the LES relax briefly in order to allow passage of food into the stomach [1]. The ME initially comprises only smooth muscle
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have