SOX9 specifies the pyloric sphincter epithelium through mesenchymal-epithelial signals.
Gastrointestinal (GI) development is highly conserved across vertebrates. Although several transcription factors and morphogenic proteins are involved in the molecular controls of GI development, the interplay between these factors is not fully understood. We report herein the expression pattern of Sox9 during GI development, and provide evidence that it functions, in part, to define the pyloric sphincter epithelium. SOX9 is expressed in the endoderm of the GI tract (with the exclusion of the gizzard) and its derivate organs, the lung and pancreas. Moreover, SOX9 is also expressed at the mesoderm of the pyloric sphincter, a structure that demarcates the gizzard from the duodenum. Using retroviral misexpression technique, we show that Sox9 expression in the pyloric sphincter is under the control of the BMP signaling pathway, known to play a key role in the development of this structure. By misexpressing SOX9 in the mesoderm of the gizzard, we show that SOX9 is able to transdifferentiate the adjacent gizzard epithelium into pyloric sphincter-like epithelium through the control of mesodermal-epithelial signals mediated in part by Gremlin (a modulator of the BMP pathway). Our results suggest that SOX9 is necessary and sufficient to specify the pyloric sphincter epithelial properties.
Moniot
Brigitte
B
Institut de Génétique Humaine, UPR 1142 CNRS, 141 rue de la Cardonille, 34396 Montpellier, Cedex 5, France.
Biau
Sandrine
S
Faure
Sandrine
S
Nielsen
Corinne M
CM
Berta
Philippe
P
Roberts
Drucilla J
DJ
de Santa Barbara
Pascal
P
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002642:Chick Embryo; D004848:Epithelium / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005895:Gizzard, Avian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D009024:Morphogenesis; D009130:Muscle, Smooth / Q000196:embryology*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011708:Pylorus / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D055758:SOX9 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D013270:Stomach / Q000033:anatomy & histology / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D006609:High Mobility Group Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors