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Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris.

  • Ali, Zaheer1
  • Cui, Dongmei2
  • Yang, Yunlong3
  • Tracey-White, Dhani4
  • Vazquez-Rodriguez, Gabriela5
  • Moosajee, Mariya4
  • Ju, Rong2
  • Li, Xuri2
  • Cao, Yihai6
  • Jensen, Lasse D7
  • 1 Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. , (Sweden)
  • 2 Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, PR China. , (China)
  • 3 Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, PR China; Institute of Pan-vascular Medicine, Fudan University, Shanghai 200032, PR China. , (China)
  • 4 Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, London, UK.
  • 5 Department of Oncology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. , (Sweden)
  • 6 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. , (Sweden)
  • 7 Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden. Electronic address: [email protected] , (Sweden)
Published Article
Developmental Biology
Publication Date
Jan 15, 2020
DOI: 10.1016/j.ydbio.2019.02.002
PMID: 30796893


The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruch's membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature. Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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