title: The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine.
abstract: The dorsal mesentery (DM) is the major conduit for blood and lymphatic vessels in the gut. The mechanisms underlying their morphogenesis are challenging to study and remain unknown. Here we show that arteriogenesis in the DM begins during gut rotation and proceeds strictly on the left side, dependent on the Pitx2 target gene Cxcl12. Although competent Cxcr4-positive angioblasts are present on the right, they fail to form vessels and progressively emigrate. Surprisingly, gut lymphatics also initiate in the left DM and arise only after-and dependent on-arteriogenesis, implicating arteries as drivers of gut lymphangiogenesis. Our data begin to unravel the origin of two distinct vascular systems and demonstrate how early left-right molecular asymmetries are translated into organ-specific vascular patterns. We propose a dual origin of gut lymphangiogenesis in which prior arterial growth is required to initiate local lymphatics that only subsequently connect to the vascular system.
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Mahadevan
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Welsh
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Aravind
authors.initials: A
authors.lastname: Sivakumar
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Gludish
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Abigail R
authors.initials: AR
authors.lastname: Shilvock
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Drew M
authors.initials: DM
authors.lastname: Noden
authors.affiliation: Developmental Neuroscience Program and Department of Radiology, Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, 4661 Sunset Boulevard, Los Angeles, CA 90027, USA.
authors.forename: David
authors.initials: D
authors.lastname: Huss
authors.affiliation: Developmental Neuroscience Program and Department of Radiology, Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, 4661 Sunset Boulevard, Los Angeles, CA 90027, USA.
authors.forename: Rusty
authors.initials: R
authors.lastname: Lansford
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. Electronic address: natasza.kurpios@cornell.edu.
authors.forename: Natasza A
authors.initials: NA
authors.lastname: Kurpios
mesh_terms: D000818:Animals; D001158:Arteries / Q000196:embryology; D019521:Body Patterning; D054377:Chemokine CXCL12 / Q000378:metabolism; D002645:Chickens; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D007422:Intestines / Q000196:embryology*; D042583:Lymphangiogenesis; D008208:Lymphatic System / Q000196:embryology*; D042601:Lymphatic Vessels / Q000196:embryology; D008643:Mesentery; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D011784:Quail; D019718:Receptors, CXCR4 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D000097577:Homeobox Protein PITX2
chemical_list: D054377:Chemokine CXCL12; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D019718:Receptors, CXCR4; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C514936:CXCR4 protein, mouse; C515256:Cxcl12 protein, mouse