Leptin signaling promotes blood vessel formation in the Xenopus tail during the embryo-larval transition

• Published in: Developmental biology 2024-08, Vol.512, p.26-34
• Main Authors: Curtis, Grace H., Reeve, Robyn E., Crespi, Erica J.
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Animals, Genetically Modified; Blood vessel; Blood Vessels - embryology; Blood Vessels - metabolism; Development; Embryo, Nonmammalian - metabolism; Gene Expression Regulation, Developmental; Green Fluorescent Proteins - metabolism; Hormone; Larva - metabolism; Leptin; Leptin - metabolism; Neovascularization, Physiologic; Signal Transduction; STAT3 Transcription Factor - metabolism; Tail - blood supply; Tail - embryology; Xenopus; Xenopus laevis - embryology; Xenopus laevis - metabolism; Xenopus Proteins - genetics; Xenopus Proteins - metabolism
• ISSN: 0012-1606; 1095-564X; 1095-564X
• DOI: 10.1016/j.ydbio.2024.05.001

The signals that regulate peripheral blood vessel formation during development are still under investigation. The hormone leptin promotes blood vessel formation, adipose tissue establishment and expansion, tumor growth, and wound healing, but the underlying mechanisms for these actions are currently unknown. We investigated whether leptin promotes angiogenesis in the developing tail fin using embryonic transgenic xflk-1:GFP Xenopus laevis, which express a green fluorescent protein on vascular endothelial cells to mark blood vessels. We found that leptin protein is expressed in endothelial cells of developing blood vessels and that leptin treatment via injection increased phosphorylated STAT3 signaling, which is indicative of leptin activation of its receptor, in blood vessels of the larval tail fin. Leptin administration via media increased vessel length, branching, and reconnection with the cardinal vein, while decreased leptin signaling via immunoneutralization had an opposing effect on vessel development. We also observed disorganization of major vessels and microvessels of the tail fin and muscle when leptin signaling was decreased. Reduced leptin signaling lowered mRNA expression of cenpk, gpx1, and mmp9, markers for cell proliferation, antioxidation, and extracellular matrix remodeling/cell migration, respectively, in the developing tail, providing insight into three possible mechanisms underlying leptin's promotion of angiogenesis. Together these results illustrate that leptin levels are correlated with embryonic angiogenesis and that leptin coordinates multiple aspects of blood vessel growth and development, showing that leptin is an important morphogen during embryonic development. [Display omitted] •Leptin protein localizes and signals in blood vessels of Xenopus embryos.•Leptin increases multiple dimensions of blood vessel growth in the tadpole tail.•Decreased leptin signaling reduces vessel growth and disrupts organization.•Leptin signaling modulates expression of proliferation and ECM remodeling genes.•First evidence linking leptin and peripheral angiogenesis in vertebrate embryos.