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Dev Biol. 2019 Aug 15;452(2):134-143. doi: 10.1016/j.ydbio.2019.05.002. Epub 2019 May 18.

Isl1-expressing non-venous cell lineage contributes to cardiac lymphatic vessel development.

Author information

1
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
2
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Department of Pediatric Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan; Department of Animal Nursing Science, Yamazaki University of Animal Health Technology, 4-7-2 Minami-osawa, Hachioji, Tokyo, 192-0364, Japan.
3
Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, 2-2-3, Minatojiima-Minamimachi, Chuou-ku, Kobe, 650-0047, Japan.
4
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo, 102-0076, Japan. Electronic address: kuri-tky@umin.net.

Abstract

The origin of the mammalian lymphatic vasculature has been studied for more than a century; however, details regarding organ-specific lymphatic development remain unknown. A recent study reported that cardiac lymphatic endothelial cells (LECs) stem from venous and non-venous origins in mice. Here, we identified Isl1-expressing progenitors as a potential non-venous origin of cardiac LECs. Genetic lineage tracing with Isl1-Cre reporter mice suggested a possible contribution from the Isl1-expressing pharyngeal mesoderm constituting the second heart field to lymphatic vessels around the cardiac outflow tract as well as to those in the facial skin and the lymph sac. Isl1+ lineage-specific deletion of Prox1 resulted in disrupted LYVE1+ vessel structures, indicating a Prox1-dependent mechanism in this contribution. Tracing back to earlier embryonic stages revealed the presence of VEGFR3+ and/or Prox1+ cells that overlapped with the Isl1+ pharyngeal core mesoderm. These data may provide insights into the developmental basis of heart diseases involving lymphatic vasculature and improve our understanding of organ-based lymphangiogenesis.

PMID:
31112709
DOI:
10.1016/j.ydbio.2019.05.002
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