ArticleFluids and barriers of the CNS2026
Role of SCF/c-KIT axis in pericyte TNT-guided vessel branching.
Article in Fluids and barriers of the CNS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIn the developing human brain, forebrain pericytes of neural crest origin are proposed to exert their function at the leading front of growing vessels. The combined sprouts are made up by an endothelial tip cell and a more advanced pericyte extended tunnelling nanotube (TNT), which forms 'intervascular bridges' during vessel branching. To better understand of the process of pericyte TNTs (P-TNTs)-guided vessel growth, we have immunolocalized the c-KIT (CD117) receptor and its ligand SCF, as a possible 'non canonical' signaling pathway involved in endothelium-pericyte interactions during the pericyte-driven mode of sprouting.
methodsImmunofluorescent high-resolution confocal microscopy and 3D modelling were applied on human developing brain and glioblastoma (GB) sections. TNTs were revealed by sequential scanning of 20-µm tissue sections, leveraging on NG2 proteoglycan as a marker of immature/re-activated pericytes and on collagen type IV (COL IV) as a TNT-associated ECM molecule. Confocal-aided morphometry was applied to evaluate the density of NG2
resultsIn both developing brain and GB samples, P-TNTs are seen associated with pericytes budding from parental vessels or advancing at the distal edge of combined vessel sprouts. The number of TNTs largely prevails in fetal brain, compared with peripheral GB areas, while it significantly reduces in tumor core areas. c-KIT
conclusionsP-TNTs, which are tightly associated in situ with endothelial-pericyte combined sprouts, appear to play a dual role during vessel collateralization by bridging the gap between distant vessels and guiding vascular outgrowth. The complementary cellular distribution of c-KIT and SCF observed in endothelial cells and pericytes suggests that both endothelial autocrine/paracrine SCF/c-KIT signaling and pericyte-derived paracrine/juxtacrine SCF cues may contribute to the pericyte-driven mode of vessel branching. Similar observations in GB samples further suggest a potential involvement of pericytes and their P-TNTs in tumor vascularization, although sprouting endothelial cells displayed distinct subcellular patterns of c-KIT expression in fetal versus GB tissues.
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