title: Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells.
abstract: The adult mouse intestine contains an intricate vascular network. The factors that control development of this network are poorly understood. Quantitative three-dimensional imaging studies revealed that a plexus of branched interconnected vessels developed in small intestinal villi during the period of postnatal development that coincides with assembly of a complex society of indigenous gut microorganisms (microbiota). To investigate the impact of this environmental transition on vascular development, we compared the capillary networks of germ-free mice with those of ex-germ-free animals colonized during or after completion of postnatal gut development. Adult germ-free mice had arrested capillary network formation. The developmental program can be restarted and completed within 10 days after colonization with a complete microbiota harvested from conventionally raised mice, or with Bacteroides thetaiotaomicron, a prominent inhabitant of the normal mouse/human gut. Paneth cells in the intestinal epithelium secrete antibacterial peptides that affect luminal microbial ecology. Comparisons of germ-free and B. thetaiotaomicron-colonized transgenic mice lacking Paneth cells established that microbial regulation of angiogenesis depends on this lineage. These findings reveal a previously unappreciated mechanism of postnatal animal development, where microbes colonizing a mucosal surface are assigned responsibility for regulating elaboration of the underlying microvasculature by signaling through a bacteria-sensing epithelial cell.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Thaddeus S
authors.initials: TS
authors.lastname: Stappenbeck
authors.forename: Lora V
authors.initials: LV
authors.lastname: Hooper
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001439:Bacteroides / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D023082:Defensins; D004167:Diphtheria Toxin / Q000494:pharmacology; D005856:Germ-Free Life; D021621:Imaging, Three-Dimensional; D007413:Intestinal Mucosa / Q000166:cytology / Q000254:growth & development; D007421:Intestine, Small / Q000098:blood supply* / Q000254:growth & development / Q000382:microbiology / Q000648:ultrastructure; D051379:Mice; D008822:Mice, Transgenic; D008871:Microvilli; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019879:Paneth Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D023084:alpha-Defensins / Q000378:metabolism*
chemical_list: D023082:Defensins; D004167:Diphtheria Toxin; D010446:Peptide Fragments; D011506:Proteins; D023084:alpha-Defensins; C107641:cryptdin 2; C029795:diphtheria toxin fragment A