The Left-Right Pitx2 Pathway Drives Organ-Specific Arterial and Lymphatic Development in the Intestine

被引:78
作者
Mahadevan, Aparna [1 ]
Welsh, Ian C. [1 ]
Sivakumar, Aravind [1 ]
Gludish, David W. [2 ]
Shilvock, Abigail R. [1 ]
Noden, Drew M. [3 ]
Huss, David [4 ,5 ]
Lansford, Rusty [4 ,5 ]
Kurpios, Natasza A. [1 ]
机构
[1] Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA
[2] Cornell Univ, Dept Microbiol & Immunol, Coll Vet Med, Ithaca, NY 14853 USA
[3] Cornell Univ, Dept Biomed Sci, Coll Vet Med, Ithaca, NY 14853 USA
[4] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Saban Res Inst,Dev Neurosci Program, Los Angeles, CA 90027 USA
[5] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dept Radiol,Saban Res Inst, Los Angeles, CA 90027 USA
关键词
CHEMOKINE RECEPTOR CXCR4; ORIGIN; VASCULATURE; SYSTEM; MOUSE; GUT; MORPHOGENESIS; ANGIOGENESIS; ZEBRAFISH; CXCL12;
D O I
10.1016/j.devcel.2014.11.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:690 / 706
页数:17
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