title: Roles for Nkx2-5 and Gata3 in the ontogeny of the murine smooth muscle gastric ligaments.
abstract: The gastric ligaments are superficial cord-like structures, located on the lesser curvature of the stomach, that extend from the pylorus to the esophagus. These ligaments have been documented in a wide variety of mammalian species, including humans, but their composition and ontogeny is unexplored. Here, we demonstrate that, during ontogeny, the gastric ligaments are first visible as extensions from a C-shaped domain of Gata3-expressing cells that surround the future pylorus; this domain will later give rise to the pyloric outer longitudinal muscle (OLM). The open ends of the C are located ventrally, and, beginning at embryonic day (E) 13.5, the ligaments grow anteriorly from these points. Whereas most other ligaments of the stomach are neurovascular in nature, the gastric ligaments are composed of smooth muscle cells that mature between E14.5 and E16.5. The gastric ligaments coexpress the transcription factors Gata3, Nkx2-5, and Sox9, and germline loss of Gata3 or conditional deletion of Nkx2-5 abrogates Sox9 expression and impairs gastric ligament smooth muscle development; similar phenotypes were previously seen in the OLM. In accord with this molecular contiguity between the OLM and gastric ligaments, three-dimensional image reconstruction highlights physical contiguity between these smooth muscle structures, suggesting that they may work together as a unit to control flexure of the pyloric region, a function similar to the ligament of Treitz at the duodenojejunal junction. These findings may have implications for our understanding of normal pyloric sphincter function, as well as the common human congenital pathology idiopathic hypertrophic pyloric stenosis.
authors: Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Ajay
authors: A
authors: Prakash
authors: Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Aaron M
authors: AM
authors: Udager
authors: Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan.
authors: David A
authors: DA
authors: Saenz
authors: Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan dgumucio@umich.edu.
authors: Deborah L
authors: DL
authors: Gumucio
mesh_terms: D000818:Animals; D050990:GATA3 Transcription Factor / Q000502:physiology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000502:physiology*; D008022:Ligaments / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000196:embryology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000096:biosynthesis; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D050990:GATA3 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D055758:SOX9 Transcription Factor; D014157:Transcription Factors
keywords: Sox9; idiopathic hypertrophic pyloric stenosis; ligament of treitz