Specialized endothelial tip cells guide neuroretina vascularization and blood-retina-barrier formation.
Dev Cell
; 56(15): 2237-2251.e6, 2021 08 09.
Article
en En
| MEDLINE
| ID: mdl-34273276
ABSTRACT
Endothelial tip cells guiding tissue vascularization are primary targets for angiogenic therapies. Whether tip cells require differential signals to develop their complex branching patterns remained unknown. Here, we show that diving tip cells invading the mouse neuroretina (D-tip cells) are distinct from tip cells guiding the superficial retinal vascular plexus (S-tip cells). D-tip cells have a unique transcriptional signature, including high TGF-ß signaling, and they begin to acquire blood-retina barrier properties. Endothelial deletion of TGF-ß receptor I (Alk5) inhibits D-tip cell identity acquisition and deep vascular plexus formation. Loss of endothelial ALK5, but not of the canonical SMAD effectors, leads to aberrant contractile pericyte differentiation and hemorrhagic vascular malformations. Oxygen-induced retinopathy vasculature exhibits S-like tip cells, and Alk5 deletion impedes retina revascularization. Our data reveal stage-specific tip cell heterogeneity as a requirement for retinal vascular development and suggest that non-canonical-TGF-ß signaling could improve retinal revascularization and neural function in ischemic retinopathy.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Retina
/
Neovascularización Retiniana
/
Receptor Tipo I de Factor de Crecimiento Transformador beta
Límite:
Animals
Idioma:
En
Revista:
Dev Cell
Asunto de la revista:
EMBRIOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos