PAX7 is required for patterning the esophageal musculature.
- Chihara D Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029 USA.
- Romer AI Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029 USA ; Graduate School of Biological Sciences, One Gustave L. Levy Place, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA ; Present address: Department of Genetics and Development, Columbia University, 701 West 168th Street, HHSC 1602, New York, NY 10032 USA.
- Bentzinger CF Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, K1H 8L6 ON Canada ; Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8M5 ON Canada ; Present address: Nestlé Institute of Health Sciences, EPFL Campus, 1015 Lausanne, Switzerland.
- Rudnicki MA Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, K1H 8L6 ON Canada ; Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8M5 ON Canada.
- Krauss RS Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY 10029 USA ; Graduate School of Biological Sciences, One Gustave L. Levy Place, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA.
- 2015-12-05
Published in:
- Skeletal muscle. - 2015
Cell proliferation
Esophageal myogenesis
Frontal expansion
Megaesophagus
Pax7
Skeletal muscle
Smooth muscle
English
BACKGROUND
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. 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.
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 (-/-) 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.
CONCLUSIONS
Postnatal 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.
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. 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.
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 (-/-) 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.
CONCLUSIONS
Postnatal 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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s13395-015-0068-0
- PMID 26635949
- Persistent URL
- https://sonar.ch/global/documents/104920
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