Bo-Gyeong Kim1, Yong Hwan Kim2, Edward L Stanley3, Eva M Garrido-Martin2, Young Jae Lee1, S Paul Oh1,2. 1. Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon 21999, Republic of Korea. 2. Department of Physiology and Functional Genomics, College of Medicine, University of Florida, 1600 SW Archer Road, Room CG-20B, Gainesville, FL 32610, USA. 3. Department of Herpetology, Florida Museum of Natural History, University of Florida, Gainesville, FL 32610, USA.
Abstract
AIMS: Chemokine CXCL12 (stromal derived factor 1: SDF1) has been shown to play important roles in various processes of cardiovascular development. In recent avian studies, CXCL12 signalling has been implicated in guidance of cardiac neural crest cells for their participation in the development of outflow tract and cardiac septum. The goal of this study is to investigate the extent to which CXCL12 signalling contribute to the development of aortic arch and pulmonary arteries in mammals. METHODS AND RESULTS: Novel Cxcl12-LacZ reporter and conditional alleles were generated. Using whole mount X-gal staining with the reporter allele and vascular casting techniques, we show that the domain branching pattern of pulmonary arteries in Cxcl12-null mice is completely disrupted and discordant with that of pulmonary veins and airways. Cxcl12-null mice also displayed abnormal and superfluous arterial branches from the aortic arch. The early steps of pharyngeal arch remodelling in Cxcl12-null mice appeared to be unaffected, but vertebral arteries were often missing and prominent aberrant arteries were present parallel to carotid arteries or trachea, similar to aberrant vertebral artery or thyroid ima artery, respectively. Analysis with computed tomography not only confirmed the results from vascular casting studies but also identified abnormal systemic arterial supply to lungs in the Cxcl12-null mice. Tie2-Cre mediated Cxcr4 deletion phenocopied the Cxcl12-null phenotypes, indicating that CXCR4 is the primary receptor for arterial patterning, whereas Cxcl12 or Cxcr4 deletion by Wnt1-Cre did not affect aortic arch patterning. CONCLUSION: CXCL12-CXCR4 signalling is essential for the correct patterning of aortic arches and pulmonary arteries during development. Superfluous arteries in Cxcl12-null lungs and the aortic arch infer a role of CXCL12 in protecting arteries from uncontrolled sprouting during development of the arterial system. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Chemokine CXCL12 (stromal derived factor 1: SDF1) has been shown to play important roles in various processes of cardiovascular development. In recent avian studies, CXCL12 signalling has been implicated in guidance of cardiac neural crest cells for their participation in the development of outflow tract and cardiac septum. The goal of this study is to investigate the extent to which CXCL12 signalling contribute to the development of aortic arch and pulmonary arteries in mammals. METHODS AND RESULTS: Novel Cxcl12-LacZ reporter and conditional alleles were generated. Using whole mount X-gal staining with the reporter allele and vascular casting techniques, we show that the domain branching pattern of pulmonary arteries in Cxcl12-null mice is completely disrupted and discordant with that of pulmonary veins and airways. Cxcl12-null mice also displayed abnormal and superfluous arterial branches from the aortic arch. The early steps of pharyngeal arch remodelling in Cxcl12-null mice appeared to be unaffected, but vertebral arteries were often missing and prominent aberrant arteries were present parallel to carotid arteries or trachea, similar to aberrant vertebral artery or thyroid ima artery, respectively. Analysis with computed tomography not only confirmed the results from vascular casting studies but also identified abnormal systemic arterial supply to lungs in the Cxcl12-null mice. Tie2-Cre mediated Cxcr4 deletion phenocopied the Cxcl12-null phenotypes, indicating that CXCR4 is the primary receptor for arterial patterning, whereas Cxcl12 or Cxcr4 deletion by Wnt1-Cre did not affect aortic arch patterning. CONCLUSION: CXCL12-CXCR4 signalling is essential for the correct patterning of aortic arches and pulmonary arteries during development. Superfluous arteries in Cxcl12-null lungs and the aortic arch infer a role of CXCL12 in protecting arteries from uncontrolled sprouting during development of the arterial system. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: U Bartram; D G Molin; L J Wisse; A Mohamad; L P Sanford; T Doetschman; C P Speer; R E Poelmann; A C Gittenberger-de Groot Journal: Circulation Date: 2001-06-05 Impact factor: 29.690
Authors: Paul M Gignac; Nathan J Kley; Julia A Clarke; Matthew W Colbert; Ashley C Morhardt; Donald Cerio; Ian N Cost; Philip G Cox; Juan D Daza; Catherine M Early; M Scott Echols; R Mark Henkelman; A Nele Herdina; Casey M Holliday; Zhiheng Li; Kristin Mahlow; Samer Merchant; Johannes Müller; Courtney P Orsbon; Daniel J Paluh; Monte L Thies; Henry P Tsai; Lawrence M Witmer Journal: J Anat Date: 2016-03-11 Impact factor: 2.610
Authors: Russell H Knutsen; Leah M Gober; Joseph R Sukinik; Danielle R Donahue; Elise K Kronquist; Mark D Levin; Sean E McLean; Beth A Kozel Journal: J Vis Exp Date: 2020-06-20 Impact factor: 1.355
Authors: Mark F Sabbagh; Jacob S Heng; Chongyuan Luo; Rosa G Castanon; Joseph R Nery; Amir Rattner; Loyal A Goff; Joseph R Ecker; Jeremy Nathans Journal: Elife Date: 2018-09-06 Impact factor: 8.140
Authors: Anna Winnicki; James Gadd; Vahagn Ohanyan; Gilbert Hernandez; Yang Wang; Molly Enrick; Hannah McKillen; Matthew Kiedrowski; Dipan Kundu; Karlina Kegecik; Marc Penn; William M Chilian; Liya Yin; Feng Dong Journal: Front Cardiovasc Med Date: 2022-09-06